Home LiteratureArticle Details
PMID: 21461859 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

Role of DDR1 in the gelatinases secretion induced by native type IV collagen in MDA-MB-231 breast cancer cells.

Clinical & experimental metastasis ·Vol. 28 ·No. 5 ·2011-06-00 ·Pages 463-77

Castro-Sanchez L, Soto-Guzman A, Guaderrama-Diaz M, Cortes-Reynosa P, Salazar EP

Abstract

Discoidin domain receptors (DDRs) are receptor tyrosine kinases that get activated by collagens in its native triple-helical form. In mammalian cells, DDR family consists of two members, namely DDR1 and DDR2, which mediates migration and proliferation of several cell types. DDR1 is activated by native type IV collagen and overexpressed in human breast cancer. Type IV collagen is the main component of basement membrane (BM), and the ability to degrade and penetrate BM is related with an increased potential for invasion and metastasis. Matrix metalloproteinases (MMPs) are a family of zinc-dependent endopeptidases that collectively are capable of degrading all components of the extracellular matrix, including the BM. In breast cancer cells, denatured type IV collagen induces MMP-9 secretion and invasion. However, the role of DDR1 in the regulation of gelatinases (MMP-2 and -9) secretion and invasion in breast cancer cells remains to be studied. We demonstrate here that native type IV collagen induces MMP-2 and -9 secretions and invasion through a DDR1 and Src-dependent pathway, together with an increase of MMP-2 and -9-cell surface levels. MMP-2 and -9 secretions require PKC kinase activity, epidermal growth factor receptor (EGFR) activation, arachidonic acid (AA) production and AA metabolites in MDA-MB-231 breast cancer cells. In summary, our data demonstrate, for the first time, that DDR1 mediates MMP-2 and -9 secretions and invasion induced by native type IV collagen in MDA-MB-231 breast cancer cells.

MeSH Terms
Breast Neoplasms/metabolism,pathology Collagen Type IV/metabolism Discoidin Domain Receptor 1 Female Humans Matrix Metalloproteinase 2/metabolism Matrix Metalloproteinase 9/metabolism Receptor Protein-Tyrosine Kinases/metabolism Tumor Cells, Cultured
Chemicals
Collagen Type IV DDR1 protein, human Discoidin Domain Receptor 1 Receptor Protein-Tyrosine Kinases Matrix Metalloproteinase 2 Matrix Metalloproteinase 9
Authors & Affiliations
5 authors, click to expand affiliations / ORCID
Castro-Sanchez Luis
Departamento de Biologia Celular, Cinvestav-IPN, San Pedro Zacatenco, 07360, Mexico, DF, Mexico.
Soto-Guzman Adriana
Guaderrama-Diaz Margarita
Cortes-Reynosa Pedro
Salazar Eduardo Perez
References (110)
110 references, click to expand
  1. Matrix metalloproteinases: molecular aspects of their roles in tumour invasion and metastasis.
    Eur J Cancer. 2000 Aug;36(13 Spec No):1621-30 PMID: 10959048
  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. Structure, function, and control of phosphoinositide-specific phospholipase C.
    Physiol Rev. 2000 Oct;80(4):1291-335 PMID: 11015615
  4. EGFR signal transactivation in cancer cells.
    Biochem Soc Trans. 2003 Dec;31(Pt 6):1203-8 PMID: 14641026
  5. Discoidin domain receptor 1 receptor tyrosine kinase induces cyclooxygenase-2 and promotes chemoresistance through nuclear factor-kappaB pathway activation.
    Cancer Res. 2006 Aug 15;66(16):8123-30 PMID: 16912190
  6. Matrix metalloproteinases: multifunctional contributors to tumor progression.
    Mol Med Today. 2000 Apr;6(4):149-56 PMID: 10740253
  7. Suppression of ICE and apoptosis in mammary epithelial cells by extracellular matrix.
    Science. 1995 Feb 10;267(5199):891-3 PMID: 7531366
  8. The 72 kDa type IV collagenase is modulated via differential expression of alpha v beta 3 and alpha 5 beta 1 integrins during human melanoma cell invasion.
    Cancer Res. 1993 Jul 15;53(14):3411-5 PMID: 7686818
  9. Elevated protein kinase C expression in human breast tumor biopsies relative to normal breast tissue.
    Cancer Res. 1989 Jun 15;49(12):3215-7 PMID: 2720675
  10. Discoidin domain receptor 1 isoform-a (DDR1alpha) promotes migration of leukocytes in three-dimensional collagen lattices.
    FASEB J. 2001 Dec;15(14):2724-6 PMID: 11606478
  11. The microenvironment of the tumour-host interface.
    Nature. 2001 May 17;411(6835):375-9 PMID: 11357145
  12. Matrix metalloproteinases in cancer: from new functions to improved inhibition strategies.
    Int J Dev Biol. 2004;48(5-6):411-24 PMID: 15349816
  13. Platelet-collagen adhesion.
    Methods Enzymol. 1982;82 Pt A:509-13 PMID: 7078447
  14. Native type IV collagen induces cell migration through a CD9 and DDR1-dependent pathway in MDA-MB-231 breast cancer cells.
    Eur J Cell Biol. 2010 Nov;89(11):843-52 PMID: 20709424
  15. EGF receptor transactivation by G-protein-coupled receptors requires metalloproteinase cleavage of proHB-EGF.
    Nature. 1999 Dec 23-30;402(6764):884-8 PMID: 10622253
  16. Isolation and characterization of a 70-kDa metalloprotease (gelatinase) that is elevated in Rous sarcoma virus-transformed chicken embryo fibroblasts.
    J Biol Chem. 1991 Mar 15;266(8):5113-21 PMID: 1848240
  17. Metastatic potential correlates with enzymatic degradation of basement membrane collagen.
    Nature. 1980 Mar 6;284(5751):67-8 PMID: 6243750
  18. Collagen stimulates discoidin domain receptor 1-mediated migration of smooth muscle cells through Src.
    Cardiovasc Pathol. 2011 Mar-Apr;20(2):71-6 PMID: 20093046
  19. Biochemical signals and biological responses elicited by the focal adhesion kinase.
    Biochim Biophys Acta. 2001 Jul 25;1540(1):1-21 PMID: 11476890
  20. Structure and biology of the globular domain of basement membrane type IV collagen.
    Ann N Y Acad Sci. 1985;460:58-72 PMID: 2421628
  21. Arachidonic acid promotes FAK activation and migration in MDA-MB-231 breast cancer cells.
    Exp Cell Res. 2008 Nov 1;314(18):3340-55 PMID: 18804105
  22. Expression of metastasis-associated mts1 gene is co-induced with membrane type-1 matrix metalloproteinase (MT1-MMP) during oncogenic transformation and tubular formation of Madin Darby canine kidney (MDCK) epithelial cells.
    Clin Exp Metastasis. 2000;18(1):51-6 PMID: 11206838
  23. src-related tyrosine kinases regulate transcriptional activation of the interstitial collagenase gene, MMP-1, in interleukin-1-stimulated synovial fibroblasts.
    Arthritis Rheum. 1996 Apr;39(4):574-82 PMID: 8630105
  24. FGF-2 and TPA induce matrix metalloproteinase-9 secretion in MCF-7 cells through PKC activation of the Ras/ERK pathway.
    Biochem Biophys Res Commun. 2002 May 17;293(4):1174-82 PMID: 12054499
  25. Matrix metalloproteinases in tumour invasion and metastasis.
    J Pathol. 1999 Nov;189(3):300-8 PMID: 10547590
  26. Matrix metalloproteinase 9 and the epidermal growth factor signal pathway in operable non-small cell lung cancer.
    Clin Cancer Res. 2000 Jun;6(6):2349-55 PMID: 10873086
  27. Discoidin domain receptors: structural relations and functional implications.
    FASEB J. 1999;13 Suppl:S77-82 PMID: 10352148
  28. An orphan receptor tyrosine kinase family whose members serve as nonintegrin collagen receptors.
    Mol Cell. 1997 Dec;1(1):25-34 PMID: 9659900
  29. Mapping of DDR1 distribution and oligomerization on the cell surface by FRET microscopy.
    J Mol Biol. 2009 Jan 16;385(2):432-45 PMID: 19007791
  30. Release of arachidonate from diglyceride in human platelets requires the sequential action of a diglyceride lipase and a monoglyceride lipase.
    Biochem Biophys Res Commun. 1981 Jun;100(4):1688-95 PMID: 7295321
  31. Expression and signaling activity of Wnt-5a/discoidin domain receptor-1 and Syk plays distinct but decisive roles in breast cancer patient survival.
    Clin Cancer Res. 2005 Jan 15;11(2 Pt 1):520-8 PMID: 15701836
  32. Overexpression of the focal adhesion kinase (p125FAK) in invasive human tumors.
    Cancer Res. 1995 Jul 1;55(13):2752-5 PMID: 7796399
  33. Activation of Src in human breast tumor cell lines: elevated levels of phosphotyrosine phosphatase activity that preferentially recognizes the Src carboxy terminal negative regulatory tyrosine 530.
    Oncogene. 1999 Feb 4;18(5):1227-37 PMID: 10022129
  34. Expression patterns of the novel receptor-like tyrosine kinase, DDR, in human breast tumours.
    Oncogene. 1995 Feb 2;10(3):569-75 PMID: 7845682
  35. Homophilic interactions of Tetraspanin CD151 up-regulate motility and matrix metalloproteinase-9 expression of human melanoma cells through adhesion-dependent c-Jun activation signaling pathways.
    J Biol Chem. 2006 Aug 25;281(34):24279-92 PMID: 16798740
  36. The collagenase of Entamoeba histolytica.
    J Exp Med. 1982 Jan 1;155(1):42-51 PMID: 6274995
  37. Matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs): Positive and negative regulators in tumor cell adhesion.
    Semin Cancer Biol. 2010 Jun;20(3):161-8 PMID: 20470890
  38. Matrix metalloproteinase inhibitors and cancer: trials and tribulations.
    Science. 2002 Mar 29;295(5564):2387-92 PMID: 11923519
  39. Role of alpha 3 beta 1 and alpha 2 beta 1 integrins in melanoma cell migration.
    Melanoma Res. 1993 Dec;3(6):435-41 PMID: 7512849
  40. Inhibition of arachidonic acid metabolism and its implication on cell proliferation and tumour-angiogenesis.
    Int Immunopharmacol. 2009 Jun;9(6):701-15 PMID: 19239926
  41. Proteinase requirements of epidermal growth factor-induced ovarian cancer cell invasion.
    Int J Cancer. 1998 Oct 29;78(3):331-7 PMID: 9766568
  42. Matrix metalloproteinase-2 involvement in breast cancer progression: a mini-review.
    Med Sci Monit. 2009 Feb;15(2):RA32-40 PMID: 19182722
  43. Arachidonic acid in cell signaling.
    Curr Opin Cell Biol. 1993 Apr;5(2):274-80 PMID: 7685181
  44. The discoidin domain receptor tyrosine kinases are activated by collagen.
    Mol Cell. 1997 Dec;1(1):13-23 PMID: 9659899
  45. Interaction of discoidin domain receptor 1 isoform b (DDR1b) with collagen activates p38 mitogen-activated protein kinase and promotes differentiation of macrophages.
    FASEB J. 2003 Jul;17(10):1286-8 PMID: 12738814
  46. Epidermal growth factor receptor tyrosine kinase. Investigation of catalytic mechanism, structure-based searching and discovery of a potent inhibitor.
    Biochem Pharmacol. 1994 Aug 17;48(4):659-66 PMID: 8080438
  47. Expression of pp60c-src protein kinase in adult and fetal human tissue: high activities in some sarcomas and mammary carcinomas.
    Cancer Res. 1983 Apr;43(4):1696-702 PMID: 6403227
  48. Regulation of motility and protease expression in PKC-mediated induction of MCF-7 breast cancer cell invasiveness.
    Exp Cell Res. 1999 Feb 25;247(1):105-13 PMID: 10047452
  49. Pyrrolidine inhibitors of human cytosolic phospholipase A(2).
    J Med Chem. 2000 Mar 23;43(6):1041-4 PMID: 10737736
  50. 15S-Lipoxygenase-2 mediates arachidonic acid-stimulated adhesion of human breast carcinoma cells through the activation of TAK1, MKK6, and p38 MAPK.
    J Biol Chem. 2005 Sep 9;280(36):31413-9 PMID: 16000313
  51. Arachidonic-acid-derived eicosanoids: roles in biology and immunopathology.
    Trends Mol Med. 2008 Oct;14(10):461-9 PMID: 18774339
  52. Multiple signaling pathways involved in activation of matrix metalloproteinase-9 (MMP-9) by heregulin-beta1 in human breast cancer cells.
    Oncogene. 2001 Dec 6;20(56):8066-74 PMID: 11781819
  53. Roles of the matrix metalloproteinases in mammary gland development and cancer.
    Breast Cancer Res Treat. 1998 Jul;50(2):97-116 PMID: 9822215
  54. The bisindolylmaleimide GF 109203X is a potent and selective inhibitor of protein kinase C.
    J Biol Chem. 1991 Aug 25;266(24):15771-81 PMID: 1874734
  55. Arachidonate metabolism and the signaling pathway of induction of apoptosis by oxidized LDL/oxysterol.
    J Lipid Res. 2001 Oct;42(10):1678-86 PMID: 11590225
  56. Prostaglandin E2 transactivates EGF receptor: a novel mechanism for promoting colon cancer growth and gastrointestinal hypertrophy.
    Nat Med. 2002 Mar;8(3):289-93 PMID: 11875501
  57. Discovery of a novel, potent, and Src family-selective tyrosine kinase inhibitor. Study of Lck- and FynT-dependent T cell activation.
    J Biol Chem. 1996 Jan 12;271(2):695-701 PMID: 8557675
  58. Effects of tetramethoxystilbene on hormone-resistant breast cancer cells: biological and biochemical mechanisms of action.
    Cancer Res. 2007 Jun 15;67(12):5717-26 PMID: 17575138
  59. Activation of the c-Src tyrosine kinase is required for the induction of mammary tumors in transgenic mice.
    Genes Dev. 1994 Jan;8(1):23-32 PMID: 7507074
  60. Src kinase regulates metalloproteinase-9 secretion induced by type IV collagen in MCF-7 human breast cancer cells.
    Matrix Biol. 2008 Apr;27(3):220-31 PMID: 18061419
  61. Inhibition of arachidonic acid metabolism decreases tumor cell invasion and matrix metalloproteinase expression.
    Prostaglandins Other Lipid Mediat. 2010 Nov;93(3-4):100-8 PMID: 20654727
  62. Cancer metastasis and angiogenesis: an imbalance of positive and negative regulation.
    Cell. 1991 Jan 25;64(2):327-36 PMID: 1703045
  63. PKC and the control of localized signal dynamics.
    Nat Rev Mol Cell Biol. 2010 Feb;11(2):103-12 PMID: 20094051
  64. Overexpression of tissue inhibitor of matrix metalloproteinases-1 (TIMP-1) in metastatic MDCK cells transformed by v-src.
    Clin Exp Metastasis. 1999 Mar;17(2):105-10 PMID: 10411101
  65. Arachidonic acid increases matrix metalloproteinase 9 secretion and expression in human monocytic MonoMac 6 cells.
    Lipids Health Dis. 2009 Mar 30;8:11 PMID: 19331685
  66. Microdomains of GPI-anchored proteins in living cells revealed by crosslinking.
    Nature. 1998 Aug 20;394(6695):802-5 PMID: 9723622
  67. The discoidin domain receptor tyrosine kinase DDR1 in arterial wound repair.
    J Clin Invest. 2001 Mar;107(6):727-35 PMID: 11254672
  68. Metalloproteinases: role in breast carcinogenesis, invasion and metastasis.
    Breast Cancer Res. 2000;2(4):252-7 PMID: 11250717
  69. Cell adhesion molecules in the normal and cancerous mammary gland.
    J Mammary Gland Biol Neoplasia. 1996 Apr;1(2):207-18 PMID: 10887494
  70. Discoidin domain receptor 1 tyrosine kinase has an essential role in mammary gland development.
    Mol Cell Biol. 2001 Apr;21(8):2906-17 PMID: 11283268
  71. Promotion of cell adhesion by single-stranded and triple-helical peptide models of basement membrane collagen alpha 1(IV)531-543. Evidence for conformationally dependent and conformationally independent type IV collagen cell adhesion sites.
    J Biol Chem. 1994 Dec 9;269(49):30939-45 PMID: 7983028
  72. Pinpointing phosphotyrosine-dependent interactions downstream of the collagen receptor DDR1.
    FEBS Lett. 2006 Jan 9;580(1):15-22 PMID: 16337946
  73. Tyrosine kinase activity of discoidin domain receptor 1 is necessary for smooth muscle cell migration and matrix metalloproteinase expression.
    Circ Res. 2002 Jun 14;90(11):1147-9 PMID: 12065315
  74. beta4 integrin-dependent formation of polarized three-dimensional architecture confers resistance to apoptosis in normal and malignant mammary epithelium.
    Cancer Cell. 2002 Sep;2(3):205-16 PMID: 12242153
  75. Extracellular matrix 6: role of matrix metalloproteinases in tumor invasion and metastasis.
    FASEB J. 1993 Dec;7(15):1434-41 PMID: 8262328
  76. Division of labor among the alpha6beta4 integrin, beta1 integrins, and an E3 laminin receptor to signal morphogenesis and beta-casein expression in mammary epithelial cells.
    Mol Biol Cell. 1999 Sep;10(9):2817-28 PMID: 10473629
  77. Matrix metalloproteinases.
    J Biol Chem. 1999 Jul 30;274(31):21491-4 PMID: 10419448
  78. Localization of matrix metalloproteinase MMP-2 to the surface of invasive cells by interaction with integrin alpha v beta 3.
    Cell. 1996 May 31;85(5):683-93 PMID: 8646777
  79. Modulation of endothelial cell expression of intercellular adhesion molecule 1 by protein kinase C activation.
    Biochem Biophys Res Commun. 1989 Jun 30;161(3):945-52 PMID: 2742593
  80. Activated integrin alphavbeta3 cooperates with metalloproteinase MMP-9 in regulating migration of metastatic breast cancer cells.
    Proc Natl Acad Sci U S A. 2003 Aug 5;100(16):9482-7 PMID: 12874388
  81. Structure and biological activity of the extracellular matrix.
    J Mol Med (Berl). 1998 Mar;76(3-4):253-65 PMID: 9535559
  82. New functions for the matrix metalloproteinases in cancer progression.
    Nat Rev Cancer. 2002 Mar;2(3):161-74 PMID: 11990853
  83. Sensing extracellular matrix: an update on discoidin domain receptor function.
    Cell Signal. 2006 Aug;18(8):1108-16 PMID: 16626936
  84. Distinct structural characteristics of discoidin I subfamily receptor tyrosine kinases and complementary expression in human cancer.
    Oncogene. 1995 Feb 2;10(3):609-18 PMID: 7845687
  85. Arachidonic acid as a bioactive molecule.
    J Clin Invest. 2001 Jun;107(11):1339-45 PMID: 11390413
  86. Activation of discoidin domain receptor 1 facilitates the maturation of human monocyte-derived dendritic cells through the TNF receptor associated factor 6/TGF-beta-activated protein kinase 1 binding protein 1 beta/p38 alpha mitogen-activated protein kinase signaling cascade.
    J Immunol. 2003 Oct 1;171(7):3520-32 PMID: 14500648
  87. MMP-2 mediates ethanol-induced invasion of mammary epithelial cells over-expressing ErbB2.
    Int J Cancer. 2006 Jul 1;119(1):8-16 PMID: 16450376
  88. Analysis of pp60c-src protein kinase activity in human tumor cell lines and tissues.
    J Biol Chem. 1986 Oct 15;261(29):13754-9 PMID: 3093483
  89. Protein kinase Cvarepsilon mediates Stat3Ser727 phosphorylation, Stat3-regulated gene expression, and cell invasion in various human cancer cell lines through integration with MAPK cascade (RAF-1, MEK1/2, and ERK1/2).
    Oncogene. 2010 May 27;29(21):3100-9 PMID: 20228845
  90. Production of matrix metalloproteinases and tissue inhibitors of metalloproteinases in human breast carcinomas.
    Jpn J Cancer Res. 1996 Jun;87(6):602-11 PMID: 8766524
  91. A renaissance for SRC.
    Nat Rev Cancer. 2004 Jun;4(6):470-80 PMID: 15170449
  92. Oleic acid promotes MMP-9 secretion and invasion in breast cancer cells.
    Clin Exp Metastasis. 2010 Oct;27(7):505-15 PMID: 20617371
  93. Extracellular matrix assembly.
    Annu Rev Cell Biol. 1988;4:183-207 PMID: 2848551
  94. Proteolysis in human breast cancer.
    Mol Pathol. 2000 Apr;53(2):99-106 PMID: 10889910
  95. Src family protein tyrosine kinases: cooperating with growth factor and adhesion signaling pathways.
    Curr Opin Cell Biol. 1997 Apr;9(2):187-92 PMID: 9069259
  96. Activation of discoidin domain receptor 1 isoform b with collagen up-regulates chemokine production in human macrophages: role of p38 mitogen-activated protein kinase and NF-kappa B.
    J Immunol. 2004 Feb 15;172(4):2332-40 PMID: 14764702
  97. Type IV collagen induces STAT5 activation in MCF7 human breast cancer cells.
    Matrix Biol. 2005 Oct;24(7):469-77 PMID: 16139998
  98. Collagen type I selectively activates ectodomain shedding of the discoidin domain receptor 1: involvement of Src tyrosine kinase.
    J Cell Biochem. 2006 Jun 1;98(3):672-84 PMID: 16440311
  99. Structure and mechanism of human cytosolic phospholipase A(2).
    Biochim Biophys Acta. 2000 Oct 31;1488(1-2):40-7 PMID: 11080675
  100. U-73122, a phospholipase C antagonist, inhibits effects of endothelin-1 and parathyroid hormone on signal transduction in UMR-106 osteoblastic cells.
    Biochim Biophys Acta. 1994 Dec 30;1224(3):575-82 PMID: 7803518
  101. AP-1 (Fra-1/c-Jun)-mediated induction of expression of matrix metalloproteinase-2 is required for 15S-hydroxyeicosatetraenoic acid-induced angiogenesis.
    J Biol Chem. 2010 May 28;285(22):16830-43 PMID: 20353950
  102. Pharmacological manipulation of cyclo-oxygenase-2 in the inflamed hydronephrotic kidney.
    Br J Pharmacol. 1996 Mar;117(6):1016-20 PMID: 8882591
  103. Control of free arachidonic acid levels by phospholipases A2 and lysophospholipid acyltransferases.
    Biochim Biophys Acta. 2009 Dec;1791(12):1103-13 PMID: 19715771
  104. Effects of 12-O-tetradecanoylphorbol-13-acetate on adhesiveness and lung-colonizing ability of Lewis lung carcinoma cells.
    Cancer Res. 1986 Jan;46(1):375-80 PMID: 3940203
  105. Cell adhesion in morphogenesis.
    Annu Rev Cell Biol. 1987;3:319-45 PMID: 3318879
  106. v-Src activates the expression of 92-kDa type IV collagenase gene through the AP-1 site and the GT box homologous to retinoblastoma control elements. A mechanism regulating gene expression independent of that by inflammatory cytokines.
    J Biol Chem. 1993 Nov 5;268(31):23460-8 PMID: 8226872
  107. Specific inhibition of cyclooxygenase-2 results in inhibition of proliferation of oral cancer cell lines via suppression of prostaglandin E2 production.
    J Oral Pathol Med. 2001 Jan;30(1):41-7 PMID: 11140899
  108. Overexpression of discoidin domain receptor 1 increases the migration and invasion of hepatocellular carcinoma cells in association with matrix metalloproteinase.
    Oncol Rep. 2007 Dec;18(6):1435-41 PMID: 17982627
  109. Protein kinase C: a novel target for inhibiting gastric cancer cell invasion.
    J Natl Cancer Inst. 1993 Mar 3;85(5):402-7 PMID: 8433394
  110. Inhibition of cyclooxygenase-2 suppresses invasiveness of oral squamous cell carcinoma cell lines via down-regulation of matrix metalloproteinase-2 and CD44.
    Clin Exp Metastasis. 2004;21(8):737-45 PMID: 16035618
Article Info
Journal
Clinical & experimental metastasis
Abbr.
Clin Exp Metastasis
ISSN
1573-7276
DOI
10.1007/s10585-011-9385-9
Published
2011-06-00
Epub
2011-00-02
Pages
463-77
Language
English
Region
Netherlands
NLM ID
8409970
Subset
IM
External Links
PubMed source DOI: 10.1007/s10585-011-9385-9 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