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PMID: 20020278 Published · ppublish English Journal Article

Cancer-stromal cell interaction and tumor angiogenesis in gastric cancer.

Cancer microenvironment : official journal of the International Cancer Microenvironment Society ·Vol. 3 ·No. 1 ·2010-12-00 ·Pages 109-16

Kitadai Y

Abstract

Recent studies in molecular and cellular biology have shown that tumor growth and metastasis are not determined by cancer cells alone but also by a variety of stromal cells. The stroma constitutes a large part of most solid tumors, and cancer-stromal cell interaction contributes functionally to tumor growth and metastasis. Angiogenesis is the result of an imbalance between positive and negative angiogenic factors released by tumor and host cells into the microenvironment of the neoplastic tissue. In gastric cancer, tumor cells and stromal cells produce various angiogenic factors, including vascular endothelial growth factor, interleukin-8, and platelet-derived endothelial cell growth factor. The microenvironment in the gastric mucosa may also influence the angiogenic phenotype of gastric cancer. Helicobacter pylori infection increases expression of several angiogenic factors by tumor cells. Activated fibroblasts and macrophages in tumor stroma also play an important role in angiogenesis and tumor progression. We review the current understanding of cancer-stromal cell interaction as it pertains to tumor angiogenesis in gastric cancer.

Authors & Affiliations
1 authors, click to expand affiliations / ORCID
Kitadai Yasuhiko
Department of Medicine and Molecular Science, Hiroshima University Graduate School of Biomedical Sciences, 1-2-3 Kasumi, Minami-ku, Hiroshima, 734-8551, Japan, kitadai@hiroshima-u.ac.jp.
References (108)
108 references, click to expand
  1. Epithelial to mesenchymal transition in human breast cancer can provide a nonmalignant stroma.
    Am J Pathol. 2003 Feb;162(2):391-402 PMID: 12547698
  2. CD40 engagement up-regulates cyclooxygenase-2 expression and prostaglandin E2 production in human lung fibroblasts.
    J Immunol. 1998 Feb 1;160(3):1053-7 PMID: 9570516
  3. Monocyte chemoattractant protein-1 expression correlates with macrophage infiltration and tumor vascularity in human esophageal squamous cell carcinomas.
    Int J Cancer. 2002 Nov 20;102(3):220-4 PMID: 12397639
  4. Helicobacter pylori infection influences expression of genes related to angiogenesis and invasion in human gastric carcinoma cells.
    Biochem Biophys Res Commun. 2003 Nov 28;311(4):809-14 PMID: 14623253
  5. Helicobacter pylori promote gastric cancer cells invasion through a NF-kappaB and COX-2-mediated pathway.
    World J Gastroenterol. 2005 Jun 7;11(21):3197-203 PMID: 15929167
  6. Helicobacter pylori infection influences tumor growth of human gastric carcinomas.
    Scand J Gastroenterol. 2003 Feb;38(2):153-8 PMID: 12678331
  7. Discovery of endothelial to mesenchymal transition as a source for carcinoma-associated fibroblasts.
    Cancer Res. 2007 Nov 1;67(21):10123-8 PMID: 17974953
  8. Genetic pathways of two types of gastric cancer.
    IARC Sci Publ. 2004;(157):327-49 PMID: 15055305
  9. Prognostic value of vascular endothelial growth factor expression in gastric carcinoma.
    Cancer. 1996 Mar 1;77(5):858-63 PMID: 8608475
  10. Tumor angiogenesis and metastasis--correlation in invasive breast carcinoma.
    N Engl J Med. 1991 Jan 3;324(1):1-8 PMID: 1701519
  11. Helicobacter pylori and atrophic gastritis: importance of the cagA status.
    J Natl Cancer Inst. 1995 Dec 6;87(23):1777-80 PMID: 7473834
  12. Friends or foes - bipolar effects of the tumour stroma in cancer.
    Nat Rev Cancer. 2004 Nov;4(11):839-49 PMID: 15516957
  13. Sustained arterial injury and progression of atherosclerosis.
    Ann N Y Acad Sci. 1990;598:223-31 PMID: 1701074
  14. Correlation of metastasis-related gene expression with metastatic potential in human prostate carcinoma cells implanted in nude mice using an in situ messenger RNA hybridization technique.
    Am J Pathol. 1997 May;150(5):1571-82 PMID: 9137084
  15. Slug is overexpressed in gastric carcinomas and may act synergistically with SIP1 and Snail in the down-regulation of E-cadherin.
    J Pathol. 2007 Apr;211(5):507-515 PMID: 17299729
  16. Stromal fibroblasts present in invasive human breast carcinomas promote tumor growth and angiogenesis through elevated SDF-1/CXCL12 secretion.
    Cell. 2005 May 6;121(3):335-48 PMID: 15882617
  17. Induction of tumor lymphangiogenesis by VEGF-C promotes breast cancer metastasis.
    Nat Med. 2001 Feb;7(2):192-8 PMID: 11175850
  18. Development of Helicobacter pylori-induced gastric carcinoma in Mongolian gerbils.
    Cancer Res. 1998 Oct 1;58(19):4255-9 PMID: 9766647
  19. Expression of interleukin-8 correlates with vascularity in human gastric carcinomas.
    Am J Pathol. 1998 Jan;152(1):93-100 PMID: 9422527
  20. Constitutive production of multiple cytokines and a human chorionic gonadotrophin beta-subunit by a human bladder cancer cell line (KU-19-19): possible demonstration of totipotential differentiation.
    Br J Cancer. 1997;76(2):163-74 PMID: 9231915
  21. Inverse expression of S100A4 and E-cadherin is associated with metastatic potential in gastric cancer.
    Clin Cancer Res. 2000 Nov;6(11):4234-42 PMID: 11106237
  22. Bone marrow contribution to tumor-associated myofibroblasts and fibroblasts.
    Cancer Res. 2004 Dec 1;64(23):8492-5 PMID: 15574751
  23. An overview of epithelio-mesenchymal transformation.
    Acta Anat (Basel). 1995;154(1):8-20 PMID: 8714286
  24. Controlled recruitment of monocytes and macrophages to specific organs through transgenic expression of monocyte chemoattractant protein-1.
    J Immunol. 1995 Dec 15;155(12):5769-76 PMID: 7499865
  25. Expression of vascular endothelial growth factor and its receptor, KDR, correlates with vascularity, metastasis, and proliferation of human colon cancer.
    Cancer Res. 1995 Sep 15;55(18):3964-8 PMID: 7664263
  26. VEGF expression by mesenchymal stem cells contributes to angiogenesis in pancreatic carcinoma.
    Br J Cancer. 2008 Aug 19;99(4):622-31 PMID: 18665180
  27. Association of ovarian malignancy with expression of platelet-derived endothelial cell growth factor.
    J Natl Cancer Inst. 1994 Aug 17;86(16):1234-8 PMID: 7518876
  28. Molecular characterization of the tumor microenvironment in breast cancer.
    Cancer Cell. 2004 Jul;6(1):17-32 PMID: 15261139
  29. Tumors: wounds that do not heal. Similarities between tumor stroma generation and wound healing.
    N Engl J Med. 1986 Dec 25;315(26):1650-9 PMID: 3537791
  30. Lymphoma-specific genetic aberrations in microvascular endothelial cells in B-cell lymphomas.
    N Engl J Med. 2004 Jul 15;351(3):250-9 PMID: 15254283
  31. Fibroblasts in cancer.
    Nat Rev Cancer. 2006 May;6(5):392-401 PMID: 16572188
  32. Induction of cyclooxygenase 2 in gastric mucosal lesions and its inhibition by the specific antagonist delays healing in mice.
    Gastroenterology. 1997 Feb;112(2):387-97 PMID: 9024292
  33. Mesenchymal stem cells: potential precursors for tumor stroma and targeted-delivery vehicles for anticancer agents.
    J Natl Cancer Inst. 2004 Nov 3;96(21):1593-603 PMID: 15523088
  34. What is the evidence that tumors are angiogenesis dependent?
    J Natl Cancer Inst. 1990 Jan 3;82(1):4-6 PMID: 1688381
  35. Macrophages, wound repair and angiogenesis.
    Prog Clin Biol Res. 1988;266:131-45 PMID: 2454496
  36. A multitargeted, metronomic, and maximum-tolerated dose "chemo-switch" regimen is antiangiogenic, producing objective responses and survival benefit in a mouse model of cancer.
    J Clin Oncol. 2005 Feb 10;23(5):939-52 PMID: 15557593
  37. Mesenchymal cells regulate the response of acute lymphoblastic leukemia cells to asparaginase.
    J Clin Invest. 2007 Apr;117(4):1049-57 PMID: 17380207
  38. Carcinoma-associated fibroblast-like differentiation of human mesenchymal stem cells.
    Cancer Res. 2008 Jun 1;68(11):4331-9 PMID: 18519693
  39. The tumor microenvironment and its role in promoting tumor growth.
    Oncogene. 2008 Oct 6;27(45):5904-12 PMID: 18836471
  40. Monocyte chemoattractant protein-1 transfection induces angiogenesis and tumorigenesis of gastric carcinoma in nude mice via macrophage recruitment.
    Clin Cancer Res. 2005 Nov 1;11(21):7629-36 PMID: 16278381
  41. Macrophages: obligate partners for tumor cell migration, invasion, and metastasis.
    Cell. 2006 Jan 27;124(2):263-6 PMID: 16439202
  42. Interleukin-8 expression in Helicobacter pylori infected, normal, and neoplastic gastroduodenal mucosa.
    J Clin Pathol. 1994 Jan;47(1):61-6 PMID: 8132812
  43. Helicobacter pylori infection induces gastric cancer in mongolian gerbils.
    Gastroenterology. 1998 Sep;115(3):642-8 PMID: 9721161
  44. Tumor cells secrete a vascular permeability factor that promotes accumulation of ascites fluid.
    Science. 1983 Feb 25;219(4587):983-5 PMID: 6823562
  45. Platelet-derived endothelial cell growth factor in human colon cancer angiogenesis: role of infiltrating cells.
    J Natl Cancer Inst. 1996 Aug 21;88(16):1146-51 PMID: 8757194
  46. Stromal fibroblasts activated by tumor cells promote angiogenesis in mouse gastric cancer.
    J Biol Chem. 2008 Jul 11;283(28):19864-71 PMID: 18495668
  47. Expression of interleukin 8 correlates with the metastatic potential of human melanoma cells in nude mice.
    Cancer Res. 1994 Jun 15;54(12):3242-7 PMID: 8205546
  48. Role of C-X-C chemokines as regulators of angiogenesis in lung cancer.
    J Leukoc Biol. 1995 May;57(5):752-62 PMID: 7539029
  49. Secretory products of macrophages.
    J Clin Invest. 1987 Feb;79(2):319-26 PMID: 3543052
  50. Circulating endothelial/skeletal progenitor cells for bone regeneration and healing.
    Bone. 2008 Sep;43(3):434-9 PMID: 18547890
  51. Prognostic importance of epithelial-mesenchymal transition-related protein expression in gastric carcinoma.
    Histopathology. 2009 Mar;54(4):442-51 PMID: 19309396
  52. Tumor-associated macrophage (TAM) infiltration in gastric cancer.
    Anticancer Res. 2003 Sep-Oct;23(5A):4079-83 PMID: 14666722
  53. TGF-beta signaling in fibroblasts modulates the oncogenic potential of adjacent epithelia.
    Science. 2004 Feb 6;303(5659):848-51 PMID: 14764882
  54. Patterns of metastases in intestinal and diffuse types of carcinoma of the stomach.
    Hum Pathol. 1981 Mar;12(3):237-42 PMID: 7228019
  55. Identification of angiogenic activity and the cloning and expression of platelet-derived endothelial cell growth factor.
    Nature. 1989 Apr 13;338(6216):557-62 PMID: 2467210
  56. Role of vascular endothelial growth factor C expression in the development of lymph node metastasis in gastric cancer.
    Clin Cancer Res. 1999 Jul;5(7):1823-9 PMID: 10430087
  57. Distinct role of macrophages in different tumor microenvironments.
    Cancer Res. 2006 Jan 15;66(2):605-12 PMID: 16423985
  58. Desmoplasia and its relevance to colorectal tumour invasion.
    Int J Cancer. 1993 Jan 2;53(1):62-9 PMID: 7677932
  59. Multilineage potential of adult human mesenchymal stem cells.
    Science. 1999 Apr 2;284(5411):143-7 PMID: 10102814
  60. Differential gene expression associated with migration of mesenchymal stem cells to conditioned medium from tumor cells or bone marrow cells.
    Stem Cells. 2007 Feb;25(2):520-8 PMID: 17053212
  61. Monocyte chemotactic protein-1 secreted by primary breast tumors stimulates migration of mesenchymal stem cells.
    Clin Cancer Res. 2007 Sep 1;13(17):5020-7 PMID: 17785552
  62. Angiogenesis in normal and psoriatic skin.
    Lab Invest. 1989 Aug;61(2):139-42 PMID: 2474088
  63. Expression of activated platelet-derived growth factor receptor in stromal cells of human colon carcinomas is associated with metastatic potential.
    Int J Cancer. 2006 Dec 1;119(11):2567-74 PMID: 16988946
  64. Cancer-related inflammation.
    Nature. 2008 Jul 24;454(7203):436-44 PMID: 18650914
  65. Expression of platelet-derived endothelial cell growth factor in Escherichia coli and confirmation of its thymidine phosphorylase activity.
    Biochemistry. 1992 Dec 8;31(48):12141-6 PMID: 1457409
  66. Epithelial-mesenchymal transitions in tumour progression.
    Nat Rev Cancer. 2002 Jun;2(6):442-54 PMID: 12189386
  67. Extent of tumor vascularization correlates with prognosis and hematogenous metastasis in gastric carcinomas.
    Cancer Res. 1996 Jun 1;56(11):2671-6 PMID: 8653715
  68. Monocyte chemoattractant protein-1 expression correlates with macrophage infiltration and tumor vascularity in human gastric carcinomas.
    Int J Oncol. 2003 Apr;22(4):773-8 PMID: 12632067
  69. Cyclo-oxygenase 2 inhibition in colorectal cancer therapy.
    Br J Surg. 2003 Sep;90(9):1055-67 PMID: 12945071
  70. Vascular-specific growth factors and blood vessel formation.
    Nature. 2000 Sep 14;407(6801):242-8 PMID: 11001067
  71. Significance of platelet-derived endothelial cell growth factor in the angiogenesis of human gastric cancer.
    Clin Cancer Res. 1998 Feb;4(2):429-34 PMID: 9516932
  72. PDGF receptors as cancer drug targets.
    Cancer Cell. 2003 May;3(5):439-43 PMID: 12781361
  73. Expression of the fms-like tyrosine kinase 4 gene becomes restricted to lymphatic endothelium during development.
    Proc Natl Acad Sci U S A. 1995 Apr 11;92(8):3566-70 PMID: 7724599
  74. Opinion: migrating cancer stem cells - an integrated concept of malignant tumour progression.
    Nat Rev Cancer. 2005 Sep;5(9):744-9 PMID: 16148886
  75. Induction of haptotactic migration of melanoma cells by neutrophil activating protein/interleukin-8.
    Biochem Biophys Res Commun. 1990 May 31;169(1):165-70 PMID: 2190552
  76. Monocyte chemoattractant protein 1 and CD40 ligation have a synergistic effect on vascular endothelial growth factor production through cyclooxygenase 2 upregulation in gastric cancer.
    J Gastroenterol. 2008;43(3):216-24 PMID: 18373164
  77. Frequent somatic mutations in PTEN and TP53 are mutually exclusive in the stroma of breast carcinomas.
    Nat Genet. 2002 Nov;32(3):355-7 PMID: 12379854
  78. Combined total genome loss of heterozygosity scan of breast cancer stroma and epithelium reveals multiplicity of stromal targets.
    Cancer Res. 2004 Oct 15;64(20):7231-6 PMID: 15492239
  79. Functions of paracrine PDGF signaling in the proangiogenic tumor stroma revealed by pharmacological targeting.
    PLoS Med. 2008 Jan 29;5(1):e19 PMID: 18232728
  80. Intracellular, intercellular, and stromal invasion of gastric mucosa, preneoplastic lesions, and cancer by Helicobacter pylori.
    Gastroenterology. 2007 Mar;132(3):1009-23 PMID: 17383424
  81. Expression of basic fibroblast growth factor in human gastric carcinomas.
    Virchows Arch B Cell Pathol Incl Mol Pathol. 1991;61(4):263-7 PMID: 1685819
  82. Angiopoietin-2 is required for postnatal angiogenesis and lymphatic patterning, and only the latter role is rescued by Angiopoietin-1.
    Dev Cell. 2002 Sep;3(3):411-23 PMID: 12361603
  83. Significance of vessel count and vascular endothelial growth factor and its receptor (KDR) in intestinal-type gastric cancer.
    Clin Cancer Res. 1996 Oct;2(10):1679-84 PMID: 9816116
  84. Blockade of vascular endothelial growth factor receptor-3 signaling inhibits fibroblast growth factor-2-induced lymphangiogenesis in mouse cornea.
    Proc Natl Acad Sci U S A. 2002 Jun 25;99(13):8868-73 PMID: 12070340
  85. Transfection of interleukin-8 increases angiogenesis and tumorigenesis of human gastric carcinoma cells in nude mice.
    Br J Cancer. 1999 Oct;81(4):647-53 PMID: 10574250
  86. Role of tumor-associated macrophages in tumor progression and invasion.
    Cancer Metastasis Rev. 2006 Sep;25(3):315-22 PMID: 16967326
  87. On the origin of cancer-associated fibroblasts.
    Cell Cycle. 2009 May 15;8(10):1461-2 PMID: 19395855
  88. Reconstruction of functionally normal and malignant human breast tissues in mice.
    Proc Natl Acad Sci U S A. 2004 Apr 6;101(14):4966-71 PMID: 15051869
  89. Activation of IL-8 gene expression by Helicobacter pylori is regulated by transcription factor nuclear factor-kappa B in gastric epithelial cells.
    J Immunol. 1998 Mar 1;160(5):2401-7 PMID: 9498783
  90. Inhibition of interleukin 8 attenuates angiogenesis in bronchogenic carcinoma.
    J Exp Med. 1994 May 1;179(5):1409-15 PMID: 7513008
  91. Tumor induction of VEGF promoter activity in stromal cells.
    Cell. 1998 Sep 18;94(6):715-25 PMID: 9753319
  92. Expression of vascular endothelial growth factor (VEGF)-C and VEGF-D in early gastric carcinoma: correlation with clinicopathological parameters.
    Cancer Lett. 2005 Aug 8;226(1):85-90 PMID: 16004935
  93. Pattern of adhesion molecule expression on vascular endothelium in Helicobacter pylori-associated antral gastritis.
    Gastroenterology. 1997 Jun;112(6):1908-19 PMID: 9178683
  94. Schistosomes, liver flukes and Helicobacter pylori. IARC Working Group on the Evaluation of Carcinogenic Risks to Humans. Lyon, 7-14 June 1994.
    IARC Monogr Eval Carcinog Risks Hum. 1994;61:1-241 PMID: 7715068
  95. Vascular endothelial growth factor and platelet-derived endothelial cell growth factor are frequently coexpressed in highly vascularized human breast cancer.
    Clin Cancer Res. 1995 Sep;1(9):961-4 PMID: 9816067
  96. Human gastrointestinal neoplasia-associated myofibroblasts can develop from bone marrow-derived cells following allogeneic stem cell transplantation.
    Stem Cells. 2009 Jun;27(6):1463-8 PMID: 19492298
  97. PDGF-BB induces intratumoral lymphangiogenesis and promotes lymphatic metastasis.
    Cancer Cell. 2004 Oct;6(4):333-45 PMID: 15488757
  98. How is blood vessel growth regulated in normal and neoplastic tissue? G.H.A. Clowes memorial Award lecture.
    Cancer Res. 1986 Feb;46(2):467-73 PMID: 2416426
  99. Differential expression of the epithelial-mesenchymal transition regulators snail, SIP1, and twist in gastric cancer.
    Am J Pathol. 2002 Nov;161(5):1881-91 PMID: 12414534
  100. Role of tissue stroma in cancer cell invasion.
    J Pathol. 2003 Jul;200(4):429-47 PMID: 12845611
  101. Targeting the expression of platelet-derived growth factor receptor by reactive stroma inhibits growth and metastasis of human colon carcinoma.
    Am J Pathol. 2006 Dec;169(6):2054-65 PMID: 17148668
  102. Paracrine signaling by platelet-derived growth factor-CC promotes tumor growth by recruitment of cancer-associated fibroblasts.
    Cancer Res. 2009 Jan 1;69(1):369-78 PMID: 19118022
  103. Cyclooxygenase-2 expression correlates with angiogenesis and apoptosis in gastric cancer tissue.
    Hum Pathol. 2004 Apr;35(4):488-95 PMID: 15116331
  104. Thymidine phosphorylase/platelet-derived endothelial cell growth factor expression associated with hepatic metastasis in gastric carcinoma.
    Br J Cancer. 1996 Apr;73(8):884-8 PMID: 8611421
  105. Stimulation of neovascularization by human rheumatoid synovial tissue macrophages.
    Arthritis Rheum. 1986 Apr;29(4):471-9 PMID: 2423091
  106. A Phase I dose-escalation study of sibrotuzumab in patients with advanced or metastatic fibroblast activation protein-positive cancer.
    Clin Cancer Res. 2003 May;9(5):1639-47 PMID: 12738716
  107. Cellular and molecular aspects of gastric cancer.
    World J Gastroenterol. 2006 May 21;12(19):2979-90 PMID: 16718776
  108. Vascular endothelial growth factor-C expression predicts lymph node metastasis of human gastric carcinomas invading the submucosa.
    Eur J Cancer. 2002 Jul;38(10):1413-9 PMID: 12091074
Article Info
Journal
Cancer microenvironment : official journal of the International Cancer Microenvironment Society
Abbr.
Cancer Microenviron
ISSN
1875-2292
DOI
10.1007/s12307-009-0032-9
Email
kitadai@hiroshima-u.ac.jp
Published
2010-12-00
Epub
2009-00-18
Pages
109-16
Language
English
Region
Netherlands
NLM ID
101322634
PMCID
PMC2970808
External Links
PubMed source DOI: 10.1007/s12307-009-0032-9 PMC Full Text
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