Home LiteratureArticle Details
PMID: 17657606 Published · ppublish English Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, Non-P.H.S. Review

Deciphering the molecular basis of breast cancer metastasis with mouse models.

Reviews in endocrine & metabolic disorders ·Vol. 8 ·No. 3 ·2007-09-00 ·Pages 199-213

Vernon AE, Bakewell SJ, Chodosh LA

Abstract

Breast cancer begins as a localized disease, but has the potential to spread to distant sites within the body. This process--known as metastasis--is the leading cause of death from breast cancer. Whether the ability of cancer cells to metastasize is an intrinsic or acquired feature is currently a topic of considerable debate. Nevertheless, the key cellular events required for metastasis are generally accepted. These include invasion of the surrounding stromal tissue, intravasation, evasion of programmed cell death, arrest within the vasculature at a distant site, extravasation, and establishment and growth within a new microenvironment. The development of mouse models that faithfully mimic critical aspects of human neoplasia has been instrumental in framing our current understanding of multistage carcinogenesis. This review examines the advantages and limitations of existing murine models for mammary carcinogenesis for probing the molecular mechanisms that contribute to metastasis, as well as non-invasive tumor imaging approaches to facilitate these investigations.

MeSH Terms
Animals Breast Neoplasms/genetics,pathology Cell Adhesion/genetics Disease Models, Animal Gene Expression Regulation, Neoplastic Mice Neoplasm Invasiveness/genetics,pathology Neoplasm Metastasis/genetics,pathology
Authors & Affiliations
3 authors, click to expand affiliations / ORCID
Vernon Ann E
Department of Cancer Biology, and The Abramson Family Cancer Research Institute, University of Pennsylvania School of Medicine, 612 BRB II/III, 421 Curie Boulevard, Philadelphia, PA 19104-6160, USA.
Bakewell Suzanne J
Chodosh Lewis A
References (208)
208 references, click to expand
  1. Intravital fluorescence videomicroscopy to study tumor angiogenesis and microcirculation.
    Neoplasia. 2000 Jan-Apr;2(1-2):53-61 PMID: 10933068
  2. Proteolytic exposure of a cryptic site within collagen type IV is required for angiogenesis and tumor growth in vivo.
    J Cell Biol. 2001 Sep 3;154(5):1069-79 PMID: 11535623
  3. The matrix metalloproteinase stromelysin-1 acts as a natural mammary tumor promoter.
    Oncogene. 2000 Feb 21;19(8):1102-13 PMID: 10713697
  4. Genetic manipulation of E-cadherin expression by epithelial tumor cells reveals an invasion suppressor role.
    Cell. 1991 Jul 12;66(1):107-19 PMID: 2070412
  5. Development of mammary hyperplasia and neoplasia in MMTV-TGF alpha transgenic mice.
    Cell. 1990 Jun 15;61(6):1147-55 PMID: 2161707
  6. The urokinase plasminogen activator system as a target for prognostic studies in breast cancer.
    Breast Cancer Res Treat. 1998;52(1-3):99-111 PMID: 10066075
  7. Nr-CAM is a target gene of the beta-catenin/LEF-1 pathway in melanoma and colon cancer and its expression enhances motility and confers tumorigenesis.
    Genes Dev. 2002 Aug 15;16(16):2058-72 PMID: 12183361
  8. Proteases and metastasis: clinical relevance nowadays?
    Curr Opin Oncol. 2005 Nov;17(6):545-50 PMID: 16224231
  9. Involvement of insulin receptor substrate 2 in mammary tumor metastasis.
    Mol Cell Biol. 2004 Nov;24(22):9726-35 PMID: 15509777
  10. RhoC is dispensable for embryogenesis and tumor initiation but essential for metastasis.
    Genes Dev. 2005 Sep 1;19(17):1974-9 PMID: 16107613
  11. Functional differentiation and alveolar morphogenesis of primary mammary cultures on reconstituted basement membrane.
    Development. 1989 Feb;105(2):223-35 PMID: 2806122
  12. CEA adhesion molecules: multifunctional proteins with signal-regulatory properties.
    Curr Opin Cell Biol. 1997 Oct;9(5):616-26 PMID: 9330864
  13. Invasion of ras-transformed breast epithelial cells depends on the proteolytic activity of cysteine and aspartic proteinases.
    Biol Chem. 2001 May;382(5):853-7 PMID: 11517941
  14. Carcinoma-associated fibroblasts direct tumor progression of initiated human prostatic epithelium.
    Cancer Res. 1999 Oct 1;59(19):5002-11 PMID: 10519415
  15. Tumor induction of VEGF promoter activity in stromal cells.
    Cell. 1998 Sep 18;94(6):715-25 PMID: 9753319
  16. The stromal proteinase MMP3/stromelysin-1 promotes mammary carcinogenesis.
    Cell. 1999 Jul 23;98(2):137-46 PMID: 10428026
  17. Angiogenesis mediated by soluble forms of E-selectin and vascular cell adhesion molecule-1.
    Nature. 1995 Aug 10;376(6540):517-9 PMID: 7543654
  18. TACE is required for the activation of the EGFR by TGF-alpha in tumors.
    EMBO J. 2003 Mar 3;22(5):1114-24 PMID: 12606576
  19. Down-regulation of cathepsin-D expression by antisense gene transfer inhibits tumor growth and experimental lung metastasis of human breast cancer cells.
    Oncogene. 2002 Aug 1;21(33):5127-34 PMID: 12140763
  20. Increased expression of ADAM family members in human breast cancer and breast cancer cell lines.
    J Cancer Res Clin Oncol. 2005 Jan;131(1):41-8 PMID: 15565459
  21. Targeted activation of beta-catenin signaling in basal mammary epithelial cells affects mammary development and leads to hyperplasia.
    Development. 2005 Jan;132(2):267-77 PMID: 15590737
  22. Tumor development is retarded in mice lacking the gene for urokinase-type plasminogen activator or its inhibitor, plasminogen activator inhibitor-1.
    Cancer Res. 2000 Oct 15;60(20):5839-47 PMID: 11059781
  23. Matrix metalloproteinases and tumor metastasis.
    Cancer Metastasis Rev. 2006 Mar;25(1):9-34 PMID: 16680569
  24. Angiogenic properties of the carcinoembryonic antigen-related cell adhesion molecule 1.
    Exp Cell Res. 2000 Nov 25;261(1):19-24 PMID: 11082271
  25. Loss of neural cell adhesion molecule induces tumor metastasis by up-regulating lymphangiogenesis.
    Cancer Res. 2004 Dec 1;64(23):8630-8 PMID: 15574770
  26. Models for studying angiogenesis in vivo.
    Int J Biol Markers. 1999 Oct-Dec;14(4):207-13 PMID: 10669948
  27. PAR1 is a matrix metalloprotease-1 receptor that promotes invasion and tumorigenesis of breast cancer cells.
    Cell. 2005 Feb 11;120(3):303-13 PMID: 15707890
  28. Matrix metalloproteinases in tumor-host cell communication.
    Differentiation. 2002 Dec;70(9-10):561-73 PMID: 12492497
  29. Effect of antihemostatic agents on experimental tumor dissemination.
    Semin Thromb Hemost. 2002 Feb;28(1):29-38 PMID: 11885023
  30. Cellular activation of the self-quenched fluorescent reporter probe in tumor microenvironment.
    Neoplasia. 2002 May-Jun;4(3):228-36 PMID: 11988842
  31. CD44v(3,8-10) is involved in cytoskeleton-mediated tumor cell migration and matrix metalloproteinase (MMP-9) association in metastatic breast cancer cells.
    J Cell Physiol. 1998 Jul;176(1):206-15 PMID: 9618160
  32. Cathepsin D in breast cancer: mechanisms and clinical applications, a 1999 overview.
    Clin Chim Acta. 2000 Feb 15;291(2):157-70 PMID: 10675721
  33. Optical imaging of matrix metalloproteinase-2 activity in tumors: feasibility study in a mouse model.
    Radiology. 2001 Nov;221(2):523-9 PMID: 11687699
  34. Bone-related genes expressed in advanced malignancies induce invasion and metastasis in a genetically defined human cancer model.
    J Biol Chem. 2003 May 2;278(18):15951-7 PMID: 12590137
  35. Transgenes expressing the Wnt-1 and int-2 proto-oncogenes cooperate during mammary carcinogenesis in doubly transgenic mice.
    Mol Cell Biol. 1992 Jan;12(1):147-54 PMID: 1530875
  36. Inactivation of the E-cadherin-mediated cell adhesion system in human cancers.
    Am J Pathol. 1998 Aug;153(2):333-9 PMID: 9708792
  37. Overexpression of the cell adhesion molecule L1 is associated with metastasis in cutaneous malignant melanoma.
    Eur J Cancer. 2002 Sep;38(13):1708-16 PMID: 12175686
  38. The adhesion molecule L1 (CD171) promotes melanoma progression.
    Int J Cancer. 2006 Aug 1;119(3):549-55 PMID: 16506207
  39. Matrix-metalloproteinases 1, 2, and 3 and their tissue inhibitors 1 and 2 in benign and malignant breast lesions: an in situ hybridization study.
    Virchows Arch. 1999 Dec;435(6):566-73 PMID: 10628798
  40. Integrins: emerging paradigms of signal transduction.
    Annu Rev Cell Dev Biol. 1995;11:549-99 PMID: 8689569
  41. In vivo molecular target assessment of matrix metalloproteinase inhibition.
    Nat Med. 2001 Jun;7(6):743-8 PMID: 11385514
  42. Direct evidence of the importance of stromal urokinase plasminogen activator (uPA) in the growth of an experimental human breast cancer using a combined uPA gene-disrupted and immunodeficient xenograft model.
    Cancer Res. 2001 Jan 15;61(2):532-7 PMID: 11212246
  43. Mammary hyperplasia and carcinoma in MMTV-cyclin D1 transgenic mice.
    Nature. 1994 Jun 23;369(6482):669-71 PMID: 8208295
  44. Macrophage-derived metalloelastase is responsible for the generation of angiostatin in Lewis lung carcinoma.
    Cell. 1997 Mar 21;88(6):801-10 PMID: 9118223
  45. Cell adhesion molecules in the development and progression of malignant melanoma.
    Cancer Metastasis Rev. 1999;18(3):345-57 PMID: 10721489
  46. Role of plasma, platelets, and endothelial cells in tumor metastasis.
    Cancer Metastasis Rev. 1984;3(2):99-114 PMID: 6386144
  47. Requirement for matrix metalloproteinase-9 (gelatinase B) expression in metastasis by murine prostate carcinoma.
    Am J Pathol. 1998 Feb;152(2):591-6 PMID: 9466586
  48. Steps in tumor metastasis: new concepts from intravital videomicroscopy.
    Cancer Metastasis Rev. 1995 Dec;14(4):279-301 PMID: 8821091
  49. Pathogenesis of bone metastasis: a review.
    J Oral Pathol Med. 2006 Mar;35(3):129-35 PMID: 16454807
  50. Integrins.
    Kidney Int Suppl. 1994 Jan;44:S17-22 PMID: 8127030
  51. Expression of matrix metalloproteinases in the microenvironment of spontaneous and experimental melanoma metastases reflects the requirements for tumor formation.
    Cancer Res. 2003 Dec 1;63(23):8221-5 PMID: 14678978
  52. Inhibition of matrix metalloproteinase 9 expression by a ribozyme blocks metastasis in a rat sarcoma model system.
    Cancer Res. 1996 Nov 15;56(22):5279-84 PMID: 8912869
  53. Differential transplantability of tumor-associated stromal cells.
    Cancer Res. 2004 Sep 1;64(17):5920-4 PMID: 15342367
  54. Matrix metalloproteinase 9 promoter activity is induced coincident with invasion during tumor progression.
    Am J Pathol. 2000 Dec;157(6):1777-83 PMID: 11106549
  55. ADAMs: modulators of cell-cell and cell-matrix interactions.
    Curr Opin Cell Biol. 2003 Oct;15(5):598-606 PMID: 14519395
  56. TGF alpha overexpression in transgenic mice induces liver neoplasia and abnormal development of the mammary gland and pancreas.
    Cell. 1990 Jun 15;61(6):1137-46 PMID: 2350785
  57. c-MYC induces mammary tumorigenesis by means of a preferred pathway involving spontaneous Kras2 mutations.
    Nat Med. 2001 Feb;7(2):235-9 PMID: 11175856
  58. Cell adhesion molecule L1 disrupts E-cadherin-containing adherens junctions and increases scattering and motility of MCF7 breast carcinoma cells.
    Cancer Res. 2006 Dec 1;66(23):11370-80 PMID: 17145883
  59. In situ analysis of breast cancer progression in murine models using a macroscopic fluorescence imaging system.
    Lasers Surg Med. 2006 Dec;38(10):928-38 PMID: 17111410
  60. Cadherin switch in tumor progression.
    Ann N Y Acad Sci. 2004 Apr;1014:155-63 PMID: 15153430
  61. Trastuzumab plus adjuvant chemotherapy for operable HER2-positive breast cancer.
    N Engl J Med. 2005 Oct 20;353(16):1673-84 PMID: 16236738
  62. Differentiation of vascular endothelium in the chick chorioallantois: a structural and autoradiographic study.
    Dev Biol. 1974 Jun;38(2):237-48 PMID: 4831108
  63. Matrix metalloproteinases in development and disease.
    Birth Defects Res C Embryo Today. 2006 Mar;78(1):1-10 PMID: 16622845
  64. Epithelial-stromal interactions and tumor progression: meeting summary and future directions.
    Cancer Res. 2001 May 1;61(9):3844-6 PMID: 11325861
  65. Formation of Neu/ErbB2-induced mammary tumors is unaffected by loss of ErbB4.
    Oncogene. 2006 Sep 14;25(41):5664-72 PMID: 16652155
  66. Noninvasive real-time imaging of apoptosis.
    Proc Natl Acad Sci U S A. 2002 Dec 24;99(26):16551-5 PMID: 12475931
  67. L1 expression as a predictor of progression and survival in patients with uterine and ovarian carcinomas.
    Lancet. 2003 Sep 13;362(9387):869-75 PMID: 13678974
  68. Cellular localization of urokinase-type plasminogen activator, its inhibitors, and their mRNAs in breast cancer tissues.
    J Pathol. 1997 Dec;183(4):388-97 PMID: 9496254
  69. Suppression of tumor growth and metastasis in Mgat5-deficient mice.
    Nat Med. 2000 Mar;6(3):306-12 PMID: 10700233
  70. Platelet and osteoclast beta3 integrins are critical for bone metastasis.
    Proc Natl Acad Sci U S A. 2003 Nov 25;100(24):14205-10 PMID: 14612570
  71. Small molecule tyrosine kinase inhibitors in the treatment of solid tumors: an update of recent developments.
    Ann Surg Oncol. 2007 Feb;14(2):942-53 PMID: 17103252
  72. Inflammation and cancer.
    Nature. 2002 Dec 19-26;420(6917):860-7 PMID: 12490959
  73. Hypoxia-inducible factor-1alpha and the glycolytic phenotype in tumors.
    Neoplasia. 2005 Apr;7(4):324-30 PMID: 15967109
  74. Heterotypic signaling between epithelial tumor cells and fibroblasts in carcinoma formation.
    Exp Cell Res. 2001 Mar 10;264(1):169-84 PMID: 11237532
  75. In vivo MRI of cancer cell fate at the single-cell level in a mouse model of breast cancer metastasis to the brain.
    Magn Reson Med. 2006 Nov;56(5):1001-10 PMID: 17029229
  76. Tumor suppressor activity of neural cell adhesion molecule in colon carcinoma.
    Am J Surg. 1997 Sep;174(3):251-7 PMID: 9324132
  77. Tissue inhibitors of metalloproteinases: evolution, structure and function.
    Biochim Biophys Acta. 2000 Mar 7;1477(1-2):267-83 PMID: 10708863
  78. Inhibition of tumor cell-induced platelet aggregation and lung metastasis by the oral GpIIb/IIIa antagonist XV454.
    Thromb Haemost. 2003 Sep;90(3):549-54 PMID: 12958625
  79. A physiologic imaging pilot study of breast cancer treated with AZD2171.
    Clin Cancer Res. 2006 Jan 1;12 (1):281-8 PMID: 16397053
  80. Metastasis: cell-autonomous mechanisms versus contributions by the tumor microenvironment.
    Cell Mol Life Sci. 2006 Feb;63(4):449-68 PMID: 16416030
  81. Humoral immunity, inflammation and cancer.
    Curr Opin Immunol. 2007 Apr;19(2):209-16 PMID: 17276050
  82. Conditional activation of Neu in the mammary epithelium of transgenic mice results in reversible pulmonary metastasis.
    Cancer Cell. 2002 Dec;2(6):451-61 PMID: 12498714
  83. N-cadherin-mediated intercellular interactions promote survival and migration of melanoma cells.
    Cancer Res. 2001 May 1;61(9):3819-25 PMID: 11325858
  84. Generation and degradation of human endostatin proteins by various proteinases.
    FEBS Lett. 2000 Dec 15;486(3):247-51 PMID: 11119712
  85. Animal models of bone metastasis.
    Cancer Treat Res. 2004;118:47-81 PMID: 15043188
  86. Cell adhesion and signalling by cadherins and Ig-CAMs in cancer.
    Nat Rev Cancer. 2004 Feb;4(2):118-32 PMID: 14964308
  87. Correlation of Snail expression with histological grade and lymph node status in breast carcinomas.
    Oncogene. 2002 May 9;21(20):3241-6 PMID: 12082640
  88. Cathepsin D: newly discovered functions of a long-standing aspartic protease in cancer and apoptosis.
    Cancer Lett. 2006 Jun 18;237(2):167-79 PMID: 16046058
  89. Matrix metalloproteinases and metastatic cancer.
    Biochem Soc Symp. 1998;63:295-313 PMID: 9513731
  90. Advances in imaging mouse tumour models in vivo.
    J Pathol. 2005 Jan;205(2):194-205 PMID: 15641018
  91. Increased primary tumor growth in mice null for beta3- or beta3/beta5-integrins or selectins.
    Proc Natl Acad Sci U S A. 2004 Jan 20;101(3):763-8 PMID: 14718670
  92. Urokinase plasminogen activator is localized in stromal cells in ductal breast cancer.
    Lab Invest. 2001 Nov;81(11):1485-501 PMID: 11706057
  93. Prognostic value of cathepsin D in breast cancer.
    Br J Cancer. 1999 Jan;79(2):189-90 PMID: 9888456
  94. Myc/p53 interactions in transgenic mouse mammary development, tumorigenesis and chromosomal instability.
    Oncogene. 1998 May 28;16(21):2755-66 PMID: 9652742
  95. Noninvasive optical tracking of red fluorescent protein-expressing cancer cells in a model of metastatic breast cancer.
    Neoplasia. 2006 Oct;8(10):796-806 PMID: 17032496
  96. MEKK1 controls matrix degradation and tumor cell dissemination during metastasis of polyoma middle-T driven mammary cancer.
    Oncogene. 2006 Aug 17;25(36):4998-5010 PMID: 16568086
  97. Reduced angiogenesis and tumor progression in gelatinase A-deficient mice.
    Cancer Res. 1998 Mar 1;58(5):1048-51 PMID: 9500469
  98. Regulation of matrix metalloproteinases: an overview.
    Mol Cell Biochem. 2003 Nov;253(1-2):269-85 PMID: 14619979
  99. E-cadherin expression in human breast cancer cells suppresses the development of osteolytic bone metastases in an experimental metastasis model.
    Cancer Res. 1996 Sep 1;56(17):4063-70 PMID: 8752180
  100. The matrix metalloproteinase matrilysin influences early-stage mammary tumorigenesis.
    Cancer Res. 1998 Dec 1;58(23):5500-6 PMID: 9850086
  101. Urokinase plasminogen activator system gene expression is increased in human breast carcinoma and its bone metastases--a comparison of normal breast tissue, non-invasive and invasive carcinoma and osseous metastases.
    Breast Cancer Res Treat. 2000 May;61(1):1-12 PMID: 10930085
  102. Acceleration of mouse mammary tumor virus-induced murine mammary tumorigenesis by a p53 172H transgene: influence of FVB background on tumor latency and identification of novel sites of proviral insertion.
    Am J Pathol. 2002 Dec;161(6):2241-53 PMID: 12466138
  103. Cadherin expression in carcinomas: role in the formation of cell junctions and the prevention of invasiveness.
    Biochim Biophys Acta. 1994 May 27;1198(1):11-26 PMID: 8199193
  104. Identification of potential anticancer drug targets through the selection of growth-inhibitory genetic suppressor elements.
    Cancer Cell. 2003 Jul;4(1):41-53 PMID: 12892712
  105. Optical imaging of cancer metastasis to bone marrow: a mouse model of minimal residual disease.
    Am J Pathol. 2002 Mar;160(3):1143-53 PMID: 11891210
  106. The distribution of secondary growths in cancer of the breast. 1889.
    Cancer Metastasis Rev. 1989 Aug;8(2):98-101 PMID: 2673568
  107. Delayed mammary tumor progression in Muc-1 null mice.
    J Biol Chem. 1995 Dec 15;270(50):30093-101 PMID: 8530414
  108. CEACAM1: a marker with a difference or more of the same?
    J Clin Oncol. 2002 Nov 1;20(21):4273-5 PMID: 12409323
  109. Mitogenic function of human procathepsin D: the role of the propeptide.
    Biochem J. 1994 Nov 1;303 ( Pt 3):775-80 PMID: 7980446
  110. A role for ADAM12 in breast tumor progression and stromal cell apoptosis.
    Cancer Res. 2005 Jun 1;65(11):4754-61 PMID: 15930294
  111. Effect of procathepsin D activation peptide on gene expression of breast cancer cells.
    Cancer Lett. 2006 Jul 28;239(1):46-54 PMID: 16168559
  112. Combined vascular and extracellular pH imaging of solid tumors.
    NMR Biomed. 2002 Apr;15(2):114-9 PMID: 11870907
  113. CEACAM1-4S, a cell-cell adhesion molecule, mediates apoptosis and reverts mammary carcinoma cells to a normal morphogenic phenotype in a 3D culture.
    Proc Natl Acad Sci U S A. 2003 Jan 21;100(2):521-6 PMID: 12522268
  114. (Make) stick and cut loose--disintegrin metalloproteases in development and disease.
    Birth Defects Res C Embryo Today. 2006 Mar;78(1):24-46 PMID: 16622847
  115. Alterations in gene expression profiles during prostate cancer progression: functional correlations to tumorigenicity and down-regulation of selenoprotein-P in mouse and human tumors.
    Cancer Res. 2002 Sep 15;62(18):5325-35 PMID: 12235003
  116. Cathepsin-D affects multiple tumor progression steps in vivo: proliferation, angiogenesis and apoptosis.
    Oncogene. 2002 Aug 29;21(38):5951-5 PMID: 12185597
  117. Roles of the matrix metalloproteinases in mammary gland development and cancer.
    Breast Cancer Res Treat. 1998 Jul;50(2):97-116 PMID: 9822215
  118. New functions for the matrix metalloproteinases in cancer progression.
    Nat Rev Cancer. 2002 Mar;2(3):161-74 PMID: 11990853
  119. Transforming growth factor beta signaling impairs Neu-induced mammary tumorigenesis while promoting pulmonary metastasis.
    Proc Natl Acad Sci U S A. 2003 Jul 8;100(14 ):8430-5 PMID: 12808151
  120. Cadherins and catenins in breast cancer.
    Curr Opin Cell Biol. 2005 Oct;17(5):499-508 PMID: 16107313
  121. Cytokine-regulated urokinase-type-plasminogen-activator (uPA) production by human breast fibroblasts in vitro.
    Breast Cancer Res Treat. 1999 May;55(1):9-20 PMID: 10472775
  122. Expression of ADAM-9 mRNA and protein in human breast cancer.
    Int J Cancer. 2003 Jul 20;105(6):754-61 PMID: 12767059
  123. Urokinase receptor antibody can reduce tumor volume and detect the presence of occult tumor metastases in vivo.
    Cancer Res. 2002 Apr 15;62(8):2390-7 PMID: 11956102
  124. Dual-color fluorescence imaging distinguishes tumor cells from induced host angiogenic vessels and stromal cells.
    Proc Natl Acad Sci U S A. 2003 Nov 25;100(24):14259-62 PMID: 14614130
  125. Targeted expression of HGF/SF in mouse mammary epithelium leads to metastatic adenosquamous carcinomas through the activation of multiple signal transduction pathways.
    Oncogene. 2003 Nov 20;22(52):8498-508 PMID: 14627990
  126. Expression of most matrix metalloproteinase family members in breast cancer represents a tumor-induced host response.
    Am J Pathol. 1996 Jul;149(1):273-82 PMID: 8686751
  127. Bioluminescent human breast cancer cell lines that permit rapid and sensitive in vivo detection of mammary tumors and multiple metastases in immune deficient mice.
    Breast Cancer Res. 2005;7(4):R444-54 PMID: 15987449
  128. Tumour-stromal interactions in breast cancer: the role of stroma in tumourigenesis.
    Tumour Biol. 2005 Jul-Aug;26(4):173-85 PMID: 16006771
  129. Cathepsin-D in primary breast cancer: prognostic evaluation involving 2810 patients.
    Br J Cancer. 1999 Jan;79(2):300-7 PMID: 9888472
  130. A novel metalloproteinase gene specifically expressed in stromal cells of breast carcinomas.
    Nature. 1990 Dec 20-27;348(6303):699-704 PMID: 1701851
  131. Urokinase-type plasminogen activator: a potent marker of metastatic potential in human cancers.
    Biochem Soc Trans. 2002 Apr;30(2):207-10 PMID: 12023852
  132. Distinct roles for cysteine cathepsin genes in multistage tumorigenesis.
    Genes Dev. 2006 Mar 1;20(5):543-56 PMID: 16481467
  133. Specialized surface protrusions of invasive cells, invadopodia and lamellipodia, have differential MT1-MMP, MMP-2, and TIMP-2 localization.
    Ann N Y Acad Sci. 1999 Jun 30;878:361-71 PMID: 10415741
  134. Hakai, a c-Cbl-like protein, ubiquitinates and induces endocytosis of the E-cadherin complex.
    Nat Cell Biol. 2002 Mar;4(3):222-31 PMID: 11836526
  135. Urokinase-type plasminogen activator system and breast cancer (Review).
    Oncol Rep. 2005 Jul;14(1):105-12 PMID: 15944776
  136. N-cadherin promotes motility in human breast cancer cells regardless of their E-cadherin expression.
    J Cell Biol. 1999 Nov 1;147(3):631-44 PMID: 10545506
  137. L1, a novel target of beta-catenin signaling, transforms cells and is expressed at the invasive front of colon cancers.
    J Cell Biol. 2005 Feb 14;168(4):633-42 PMID: 15716380
  138. A causal role for E-cadherin in the transition from adenoma to carcinoma.
    Nature. 1998 Mar 12;392(6672):190-3 PMID: 9515965
  139. Reduced expression of neural cell adhesion molecule induces metastatic dissemination of pancreatic beta tumor cells.
    Nat Med. 1999 Mar;5(3):286-91 PMID: 10086383
  140. Real-time imaging of lymphogenic metastasis in orthotopic human breast cancer.
    Cancer Res. 2006 Aug 15;66(16):8037-41 PMID: 16912179
  141. In vivo imaging of tumors with protease-activated near-infrared fluorescent probes.
    Nat Biotechnol. 1999 Apr;17(4):375-8 PMID: 10207887
  142. Histopathology of salivary and mammary gland tumors in transgenic mice expressing a human Ha-ras oncogene.
    Cancer Res. 1991 Jul 15;51(14):3762-7 PMID: 2065330
  143. Breast cancer cells induce stromal fibroblasts to express MMP-9 via secretion of TNF-alpha and TGF-beta.
    J Cell Sci. 2005 May 15;118(Pt 10):2143-53 PMID: 15855236
  144. Tumor cell-platelet interaction in metastatic disease.
    Haemostasis. 2001;31 Suppl 1:55-8 PMID: 11990481
  145. Involvement of cathepsins in the invasion, metastasis and proliferation of cancer cells.
    J Med Invest. 2005 Feb;52(1-2):1-9 PMID: 15751268
  146. Molecular imaging in living subjects: seeing fundamental biological processes in a new light.
    Genes Dev. 2003 Mar 1;17(5):545-80 PMID: 12629038
  147. Reduced metastasis of Polyoma virus middle T antigen-induced mammary cancer in plasminogen-deficient mice.
    Oncogene. 1998 Jun 18;16(24):3097-104 PMID: 9671388
  148. E-cadherin transfection down-regulates the epidermal growth factor receptor and reverses the invasive phenotype of human papilloma virus-transfected keratinocytes.
    Cancer Res. 1996 Nov 15;56(22):5285-92 PMID: 8912870
  149. Expression of the int-1 gene in transgenic mice is associated with mammary gland hyperplasia and adenocarcinomas in male and female mice.
    Cell. 1988 Nov 18;55(4):619-25 PMID: 3180222
  150. Arterial microvascularization and breast cancer colonization in bone.
    Histol Histopathol. 1997 Oct;12(4):1145-9 PMID: 9302573
  151. Protein and mRNA expression of uPAR and PAI-1 in myoepithelial cells of early breast cancer lesions and normal breast tissue.
    Br J Cancer. 2004 Aug 2;91(3):564-71 PMID: 15226768
  152. The many faces of metalloproteases: cell growth, invasion, angiogenesis and metastasis.
    Trends Cell Biol. 2001 Nov;11(11):S37-43 PMID: 11684441
  153. Distant metastasis in breast cancer: molecular mechanisms and therapeutic targets.
    Cancer Biol Ther. 2003 Jan-Feb;2(1):14-21 PMID: 12673112
  154. Delta N89 beta-catenin induces precocious development, differentiation, and neoplasia in mammary gland.
    J Cell Biol. 2001 Apr 30;153(3):555-68 PMID: 11331306
  155. The influence of matrix metalloproteinase-7 on early mammary tumorigenesis in the multiple intestinal neoplasia mouse.
    Oncol Rep. 2004 Jul;12(1):13-7 PMID: 15201952
  156. A peptide derived from the nonreceptor binding region of urokinase plasminogen activator (uPA) inhibits tumor progression and angiogenesis and induces tumor cell death in vivo.
    FASEB J. 2000 Jul;14(10):1400-10 PMID: 10877833
  157. In vivo analysis of mammary and non-mammary tumorigenesis in MMTV-cyclin D1 transgenic mice deficient in p53.
    Transgenic Res. 2001 Oct;10(5):471-8 PMID: 11708657
  158. ADAM 12 cleaves extracellular matrix proteins and correlates with cancer status and stage.
    J Biol Chem. 2004 Dec 3;279(49):51323-30 PMID: 15381692
  159. Experimental metastasis is suppressed in MMP-9-deficient mice.
    Clin Exp Metastasis. 1999 Mar;17(2):177-81 PMID: 10411111
  160. Epigenetic versus genetic alterations in the inactivation of E-cadherin.
    Semin Cancer Biol. 2002 Oct;12(5):373-9 PMID: 12191636
  161. Matrix metalloproteinases in angiogenesis: a moving target for therapeutic intervention.
    J Clin Invest. 1999 May;103(9):1237-41 PMID: 10225966
  162. Comparison of potential biological markers cathepsin B, cathepsin L, stefin A and stefin B with urokinase and plasminogen activator inhibitor-1 and clinicopathological data of breast carcinoma patients.
    Cancer Detect Prev. 2002;26(1):42-9 PMID: 12088202
  163. Overexpression of TGF alpha in transgenic mice: induction of epithelial hyperplasia, pancreatic metaplasia, and carcinoma of the breast.
    Cell. 1990 Jun 15;61(6):1121-35 PMID: 1693546
  164. Metastasizing mammary carcinomas in H19 enhancers-Igf2 transgenic mice.
    J Exp Zool. 1998 May 1;281(1):43-57 PMID: 9571768
  165. Suppression of tumorigenicity of breast cancer cells by an epithelial cell adhesion molecule (C-CAM1): the adhesion and growth suppression are mediated by different domains.
    Oncogene. 1997 Apr 10;14(14):1697-704 PMID: 9135071
  166. Cell adhesion in tumor invasion and metastasis: loss of the glue is not enough.
    Biochim Biophys Acta. 2001 Nov 30;1552(1):39-45 PMID: 11781114
  167. Ron receptor signaling augments mammary tumor formation and metastasis in a murine model of breast cancer.
    Cancer Res. 2005 Feb 15;65(4):1285-93 PMID: 15735014
  168. Urokinase plasminogen activator: a prognostic marker in multiple types of cancer.
    J Surg Oncol. 1999 Jun;71(2):130-5 PMID: 10389872
  169. Membrane-type-1 matrix metalloproteinase confers tumorigenicity on nonmalignant epithelial cells.
    Oncogene. 2005 Mar 3;24(10):1689-97 PMID: 15608664
  170. Scaling down imaging: molecular mapping of cancer in mice.
    Nat Rev Cancer. 2002 Jan;2(1):11-8 PMID: 11902581
  171. Mechanical entrapment is insufficient and intercellular adhesion is essential for metastatic cell arrest in distant organs.
    Neoplasia. 2005 May;7(5):522-7 PMID: 15967104
  172. Expression profile analysis in multiple human tumors identifies L1 (CD171) as a molecular marker for differential diagnosis and targeted therapy.
    Hum Pathol. 2006 Aug;37(8):1000-8 PMID: 16867862
  173. Cathepsin B, a prognostic indicator in lymph node-negative breast carcinoma patients: comparison with cathepsin D, cathepsin L, and other clinical indicators.
    Clin Cancer Res. 2000 Feb;6(2):578-84 PMID: 10690542
  174. Imaging of differential protease expression in breast cancers for detection of aggressive tumor phenotypes.
    Radiology. 2002 Mar;222(3):814-8 PMID: 11867806
  175. Exogenous expression of N-cadherin in breast cancer cells induces cell migration, invasion, and metastasis.
    J Cell Biol. 2000 Feb 21;148(4):779-90 PMID: 10684258
  176. Enhanced pathological angiogenesis in mice lacking beta3 integrin or beta3 and beta5 integrins.
    Nat Med. 2002 Jan;8(1):27-34 PMID: 11786903
  177. Antimetastatic effect of tinzaparin, a low-molecular-weight heparin.
    J Thromb Haemost. 2003 Sep;1(9):1972-6 PMID: 12941039
  178. Overexpression of membrane-type matrix metalloproteinase-1 gene induces mammary gland abnormalities and adenocarcinoma in transgenic mice.
    Cancer Res. 2001 Feb 1;61(3):984-90 PMID: 11221894
  179. Adhesion-independent mechanism for suppression of tumor cell invasion by E-cadherin.
    J Cell Biol. 2003 Jun 23;161(6):1191-203 PMID: 12810698
  180. Expression of a truncated Int3 gene in developing secretory mammary epithelium specifically retards lobular differentiation resulting in tumorigenesis.
    Cancer Res. 1996 Apr 15;56(8):1775-85 PMID: 8620493
  181. Matrix metalloproteinases in cancer: from new functions to improved inhibition strategies.
    Int J Dev Biol. 2004;48(5-6):411-24 PMID: 15349816
  182. The neural cell adhesion molecule L1 potentiates integrin-dependent cell migration to extracellular matrix proteins.
    J Neurosci. 2002 Jun 15;22(12 ):4918-31 PMID: 12077189
  183. Somatic inactivation of E-cadherin and p53 in mice leads to metastatic lobular mammary carcinoma through induction of anoikis resistance and angiogenesis.
    Cancer Cell. 2006 Nov;10(5):437-49 PMID: 17097565
  184. Ectodomain shedding of L1 adhesion molecule promotes cell migration by autocrine binding to integrins.
    J Cell Biol. 2001 Nov 12;155(4):661-73 PMID: 11706054
  185. Extracellular signal-regulated kinase (ERK)-dependent gene expression contributes to L1 cell adhesion molecule-dependent motility and invasion.
    J Biol Chem. 2004 Jul 9;279(28):28880-8 PMID: 15128735
  186. Receptor for urokinase is present in tumor-associated macrophages in ductal breast carcinoma.
    Cancer Res. 1993 Apr 15;53(8):1911-5 PMID: 8385573
  187. Progression to malignancy in the polyoma middle T oncoprotein mouse breast cancer model provides a reliable model for human diseases.
    Am J Pathol. 2003 Nov;163(5):2113-26 PMID: 14578209
  188. Metastatic ability of MXT mouse mammary subpopulations correlates with clonal expression and/or membrane-association of gelatinase A.
    Mol Carcinog. 1997 May;19(1):54-66 PMID: 9180929
  189. Anti-human procathepsin D activation peptide antibodies inhibit breast cancer development.
    Breast Cancer Res Treat. 1999 Oct;57(3):261-9 PMID: 10617302
  190. Metalloproteinases: role in breast carcinogenesis, invasion and metastasis.
    Breast Cancer Res. 2000;2(4):252-7 PMID: 11250717
  191. Reduced metastasis of transgenic mammary cancer in urokinase-deficient mice.
    Int J Cancer. 2005 Feb 10;113(4):525-32 PMID: 15472905
  192. Macrophages: obligate partners for tumor cell migration, invasion, and metastasis.
    Cell. 2006 Jan 27;124(2):263-6 PMID: 16439202
  193. Gelatinase A, membrane type 1 matrix metalloproteinase, and extracellular matrix metalloproteinase inducer mRNA expression: correlation with invasive growth of breast cancer.
    World J Surg. 2000 Mar;24(3):334-40 PMID: 10658069
  194. The cell-cell adhesion receptor Mel-CAM acts as a tumor suppressor in breast carcinoma.
    Am J Pathol. 1997 Sep;151(3):745-51 PMID: 9284823
  195. Models of breast cancer: is merging human and animal models the future?
    Breast Cancer Res. 2004;6(1):22-30 PMID: 14680482
  196. Coexpression of MMTV/v-Ha-ras and MMTV/c-myc genes in transgenic mice: synergistic action of oncogenes in vivo.
    Cell. 1987 May 22;49(4):465-75 PMID: 3032456
  197. Matrix metalloproteinase-9 triggers the angiogenic switch during carcinogenesis.
    Nat Cell Biol. 2000 Oct;2(10):737-44 PMID: 11025665
  198. Matrix metalloproteinases in tumor invasion and metastasis.
    Semin Cancer Biol. 2000 Dec;10(6):415-33 PMID: 11170864
  199. Colony-stimulating factor 1 promotes progression of mammary tumors to malignancy.
    J Exp Med. 2001 Mar 19;193(6):727-40 PMID: 11257139
  200. Towards third generation matrix metalloproteinase inhibitors for cancer therapy.
    Br J Cancer. 2006 Apr 10;94(7):941-6 PMID: 16538215
  201. Induction of mammary tumors by expression of polyomavirus middle T oncogene: a transgenic mouse model for metastatic disease.
    Mol Cell Biol. 1992 Mar;12(3):954-61 PMID: 1312220
  202. Suppression of prostate cancer invasive potential and matrix metalloproteinase activity by E-cadherin transfection.
    Cancer Res. 1999 Aug 1;59(15):3552-6 PMID: 10446959
  203. Smoldering and polarized inflammation in the initiation and promotion of malignant disease.
    Cancer Cell. 2005 Mar;7(3):211-7 PMID: 15766659
  204. Interactions between tumour cells and stromal cells and proteolytic modification of the extracellular matrix by metalloproteinases in cancer.
    Eur J Cancer. 2000 Jun;36(10):1258-68 PMID: 10882864
  205. The colony forming efficiency of single cells and cell aggregates from a spontaneous mouse mammary tumour using the lung colony assay.
    Br J Cancer. 1974 Oct;30(4):332-6 PMID: 4141261
  206. Involvement of integrin alpha(v)beta(3) and cell adhesion molecule L1 in transendothelial migration of melanoma cells.
    Mol Biol Cell. 2001 Sep;12 (9):2699-710 PMID: 11553709
  207. Efficient inhibition of intra-peritoneal tumor growth and dissemination of human ovarian carcinoma cells in nude mice by anti-L1-cell adhesion molecule monoclonal antibody treatment.
    Cancer Res. 2006 Jan 15;66(2):936-43 PMID: 16424028
  208. Expression of the neu protooncogene in the mammary epithelium of transgenic mice induces metastatic disease.
    Proc Natl Acad Sci U S A. 1992 Nov 15;89(22):10578-82 PMID: 1359541
Article Info
Journal
Reviews in endocrine & metabolic disorders
Abbr.
Rev Endocr Metab Disord
ISSN
1389-9155
DOI
10.1007/s11154-007-9041-5
Published
2007-09-00
Pages
199-213
Language
English
Region
Germany
NLM ID
100940588
Subset
IM
Grants
NCI NIH HHS · CA105490 · United States
NCI NIH HHS · CA98371 · United States
NICHD NIH HHS · HD050067 · United States
External Links
PubMed source DOI: 10.1007/s11154-007-9041-5 View journal details
Analysis Services
Analysis Services

Contact

No. 2 Wenbo Road, Zhangqiu District, Jinan, Shandong

Qilu Normal University · Genelibs Bioinformatics Lab

750 Shunhua Rd, Jinan

2F, Bldg F, University Science Park

Tel: 0531-88819269

WeChat Official Account

Follow our WeChat subscription account for real-time updates and the latest in medical and biological research.


Business Email

E-mail: product@genelibs.com

Copyright © 2026.Genelibs Jinan Honghui Biotechnology Co., Ltd. 鲁ICP备20007159号-2