Skip to main content

Gastric Tumor Microenvironment

  • Chapter
  • First Online:
Tumor Microenvironments in Organs

Part of the book series: Advances in Experimental Medicine and Biology ((AEMB,volume 1226))

Abstract

A compelling body of evidence has demonstrated that gastric cancer has a very particular tumor microenvironment, a signature very suitable to promote tumor progression and metastasis. Recent investigations have provided new insights into the multiple molecular mechanisms, defined by genetic and epigenetic mechanisms, supporting a very active cross talk between the components of the tumor microenvironment and thus defining the fate of tumor progression. In this review, we intend to highlight the roleĀ of very active contributors at gastric cancer TME, particularly cancer-associated fibroblasts, bone marrow-derived cells, tumor-associated macrophages, and tumor-infiltrating neutrophils, all of them surrounded by an overtime changing extracellular matrix. In addition, the very active cross talk between the components of the tumor microenvironment, defined by genetic and epigenetic mechanisms, thus defining the fate of tumor progression, is also reviewed.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 149.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 199.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 199.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  1. Van Cutsem E, Sagaert X, Topal B, Haustermans K, Prenen H (2016) Gastric cancer. Lancet 388:2654ā€“2664. https://doi.org/10.1016/S0140-6736(16)30354-3.

    ArticleĀ  PubMedĀ  Google ScholarĀ 

  2. Ferro A, Peleteiro B, Malvezzi M, Bosetti C, Bertuccio P, Levi F, Negri E, La Vecchia C, Lunet N (2014) Worldwide trends in gastric cancer mortality (1980ā€“2011), with predictions to 2015, and incidence by subtype. Eur J Cancer 2014;50(7):1330ā€“1344.

    ArticleĀ  PubMedĀ  Google ScholarĀ 

  3. Working Group on the Evaluation of Carcinogenic Risks to Humans. H. pylori Schistosomes, Liver flukes, and H. pylori views and expert opinions of an IARC Working Group On The Evaluation of Carcinogenic Risks To Humans 1994, Lyon, IARC, pp 177ā€“240

    Google ScholarĀ 

  4. Hooi JKY, Lai WY, Ng WK, Suen MMY, Underwood FE, Tanyingoh D, Malfertheiner P, Graham DY, Wong VWS, Wu JCY, Chan FKL, Sung JJY, Kaplan GG, Ng SC (2017) Global prevalence of H. pylori infection: systematic review and meta-analysis. Gastroenterology 153(2):420ā€“429

    ArticleĀ  PubMedĀ  Google ScholarĀ 

  5. Uemura N, Okamoto S, Yamamoto S, Matsumura N, Yamaguchi S, Yamakido M, Taniyama K, Sasaki N, Schlemper RJ (2001) Helicobacter pylori infection and the development of gastric cancer. N Engl J Med 345:784ā€“789

    ArticleĀ  CASĀ  PubMedĀ  Google ScholarĀ 

  6. Munn LL (2016) Cancer and inflammation. Wiley Interdiscip Rev Syst Biol Med 9(2). https://doi.org/10.1002/wsbm.1370

    Google ScholarĀ 

  7. Elkahwaji JE, Zhong W, Hopkins WJ, Bushman W (2007) Chronic bacterial infection and inflammation incite reactive hyperplasia in a mouse model of chronic prostatitis. Prostate 67:14ā€“21

    ArticleĀ  PubMedĀ  Google ScholarĀ 

  8. Herszenyi L, Miheller P, Tulassay Z (2007) Carcinogenesis in inflammatory bowel disease. Dig Dis 25:267ā€“269

    ArticleĀ  PubMedĀ  Google ScholarĀ 

  9. Li Y, Zhang J, Ma H (2014) Chronic inflammation and gallbladder cancer. Cancer Lett 345(2):242ā€“248

    ArticleĀ  CASĀ  PubMedĀ  Google ScholarĀ 

  10. Quail DF, Joyce JA (2013) Microenvironmental regulation of tumor progression and metastasis. Nat Med 19(11):1423ā€“1437

    ArticleĀ  CASĀ  PubMedĀ  PubMed CentralĀ  Google ScholarĀ 

  11. Reya T, Morrison SJ, Clarke MF (2001) Stem cells, cancer, and cancer stem cells. Nature 414:105ā€“111

    ArticleĀ  CASĀ  PubMedĀ  Google ScholarĀ 

  12. Houghton J, Stoicov C, Nomura S, Rogers AB, Carlson J, Li H, Cai X, Fox JG, Goldenring JR, Wang TC (2004) Gastric cancer originating from bone marrow-derived cells. Science 306(5701):1568ā€“1571

    ArticleĀ  CASĀ  PubMedĀ  Google ScholarĀ 

  13. Hayakawa Y, Fox JG, Wang TC (2017) The origins of gastric cancer from gastric stem cells: lessons from mouse models. Cell Mol Gastroenterol Hepatol 3(3):331ā€“338

    ArticleĀ  PubMedĀ  PubMed CentralĀ  Google ScholarĀ 

  14. Li HC, Stoicov C, Rogers AB, Houghton JM (2006) Stem cells and cancer: Evidence for bone marrow stem cells in epithelial cancers. World J Gastroenterol 12(3):363ā€“371

    ArticleĀ  PubMedĀ  PubMed CentralĀ  Google ScholarĀ 

  15. Lee HJ, Song IC, Yun HJ, Jo DY, Kim S (2014) CXC chemokines and chemokine receptors in gastric cancer: from basic findings towards therapeutic targeting. World J Gastroenterol 20(7):1681ā€“1693

    ArticleĀ  CASĀ  PubMedĀ  PubMed CentralĀ  Google ScholarĀ 

  16. Lee HJ, Jo DY (2012) The role of the CXCR4/CXCL12 axis and its clinical implications in gastric cancer. Histol Histopathol 27(9):1155ā€“1161

    CASĀ  PubMedĀ  Google ScholarĀ 

  17. Kopp HG, Ramos CA, Rafii S (2006) Contribution of endothelial progenitors and proangiogenic hematopoietic cells to vascularization of the tumor and ischemic tissue. Curr Opin Hematol 13:175ā€“181

    ArticleĀ  CASĀ  PubMedĀ  PubMed CentralĀ  Google ScholarĀ 

  18. Li B, Sharpe EE, Maupin AB, Teleron AA, Pyle AL, Carmeliet P, Young PP (2006) VEGF and PlGF promote adult vasculogenesis by enhancing EPC recruitment and vessel formation at the site of tumor neovascularization. FASEB J 20(9):1495ā€“1497

    ArticleĀ  CASĀ  PubMedĀ  Google ScholarĀ 

  19. Direkze NC, Hodivala-Dilke K, Jeffery R, Hunt T, Poulsom R, Oukrif D, Alison MR, Wright NA (2004) Bone marrow contribution to tumor-associated myofibroblasts and fibroblasts. Cancer Res 64(23):8492ā€“8495

    ArticleĀ  CASĀ  PubMedĀ  Google ScholarĀ 

  20. Maciel TT, Moura IC, Hermine O (2015) The role of mast cells in cancers, F1000. Prime Rep 7:9

    Google ScholarĀ 

  21. Molin D, Edstrom A, Glimelius I, Glimelius B, Nilsson G, Sundstrom C, Enblad G (2002) Mast cell infiltration correlates with poor prognosis in Hodgkinā€™s lymphoma. Br J Haematol 119(1):122ā€“124

    ArticleĀ  PubMedĀ  Google ScholarĀ 

  22. Ribatti D, Guidolin D, Marzullo A, Nico B, Annese T, Benagiano V, Crivellato E (2010) Mast cells and angiogenesis in gastric carcinoma. Int J Exp Pathol 91(4):350ā€“356

    ArticleĀ  CASĀ  PubMedĀ  PubMed CentralĀ  Google ScholarĀ 

  23. Zhong B, Li Y, Liu X, Wang D (2017) Association of mast cell infiltration with gastric cancer progression. Oncol Lett 15(1):755ā€“764

    PubMedĀ  PubMed CentralĀ  Google ScholarĀ 

  24. Lv Y, Zhao Y, Wang X, Chen N, Mao F, Teng Y, Wang T, Peng L, Zhang J, Cheng P, Liu Y, Kong H, Chen W, Hao C, Han B, Ma Q, Zou Q, Chen J, Zhuang Y (2019) Increased intratumoral mast cells foster immune suppression and gastric cancer progression through TNF-Ī±-PD-L1 pathway. J Immunother Cancer 7(1):54

    ArticleĀ  PubMedĀ  PubMed CentralĀ  Google ScholarĀ 

  25. Ammendola M, Patruno R, Sacco R, Marech I, Sammarco G, ZuccalĆ  V, Luposella M, Zizzo N, Gadaleta C, Porcelli M, Gadaleta CD, Ribatti D, Ranieri G (2016) Mast cells positive to tryptase and tumor-associated macrophages correlate with angiogenesis in locally advanced colorectal cancer patients undergone surgery. Expert Opin Ther Targets 20(5):533ā€“540

    ArticleĀ  CASĀ  PubMedĀ  Google ScholarĀ 

  26. Liu J, Zhang Y, Zhao J, Yang Z, Li D, Katirai F, Huang B (2011) Mast cell: insight into remodeling a tumor microenvironment. Cancer Metastasis Rev 30(2):177ā€“184

    ArticleĀ  PubMedĀ  CASĀ  Google ScholarĀ 

  27. Liu X, Jin H, Zhang G, Lin X, Chen C, Sun J, Zhang Y, Zhang Q, Yu J (2014) Intratumor IL-17 positive mast cells are the major source of the IL-17 that is predictive of survival in gastric cancer patients. PLoS One 9(9):e106834

    ArticleĀ  PubMedĀ  PubMed CentralĀ  CASĀ  Google ScholarĀ 

  28. Iida T, Iwahashi M, Katsuda M, Ishida K, Nakamori M, Nakamura M, Naka T, Ojima T, Ueda K, Hayata K, Nakamura Y, Yamaue H (2011) Tumor-infiltrating CD4+ Th17 cells produce IL-17 in the tumor microenvironment and promote tumor progression in human gastric cancer. Oncol Rep 25(5):1271ā€“1277

    CASĀ  PubMedĀ  Google ScholarĀ 

  29. Kennedy CL, Najdovska M, Jones GW, McLeod L, Hughes NR, Allison C, Ooi CH, Tan P, Ferrero RL, Jones SA, Dev A, Sievert W, Bhathal PS, Jenkins BJ (2011) The molecular pathogenesis of STAT3-driven gastric tumourigenesis in mice is independent of IL-17. J Pathol 225(2):255ā€“264

    ArticleĀ  CASĀ  PubMedĀ  Google ScholarĀ 

  30. Yang B, Kang H, Fung A, Zhao H, Wang T, Ma D The role of interleukin 17 in tumor proliferation, angiogenesis, and metastasis. Mediators Inflamm 2014, 2014:623759

    Google ScholarĀ 

  31. Numasaki M, Fukushi J, Ono M, Narula SK, Zavodny PJ, Kudo T, Robbins PD, Tahara H, Lotze MT (2003) Interleukin-17 promotes angiogenesis and tumor growth. Blood 101(7):2620ā€“2627

    ArticleĀ  CASĀ  PubMedĀ  Google ScholarĀ 

  32. Ribatti D, Ranieri G (2015) Tryptase, a novel angiogenic factor stored in mast cell granules. Exp Cell Res 332(2):157ā€“162

    ArticleĀ  CASĀ  PubMedĀ  Google ScholarĀ 

  33. de Souza Junior DA, Santana AC, da Silva EZ, Oliver C, Jamur MC (2015) The role of mast cell-specific chymases and tryptases in tumor angiogenesis. Biomed Res In 2015:142359

    Google ScholarĀ 

  34. de Souza DA Jr, Toso VD, Campos MR, Lara VS, Oliver C, Jamur MC (2012) Expression of mast cell proteases correlates with mast cell maturation and angiogenesis during tumor progression. PLoS One 7(7):e40790

    ArticleĀ  PubMedĀ  PubMed CentralĀ  CASĀ  Google ScholarĀ 

  35. Sazeides C, Le A (2018) Metabolic relationship between cancer-associated fibroblasts and cancer cells. Adv Exp Med Biol 1063:149ā€“165

    ArticleĀ  CASĀ  PubMedĀ  Google ScholarĀ 

  36. Yan Y, Wang LF, Wang RF (2015) Role of cancer-associated fibroblasts in invasion and metastasis of gastric cancer. World J Gastroenterol 21(33):9717ā€“9726

    ArticleĀ  CASĀ  PubMedĀ  PubMed CentralĀ  Google ScholarĀ 

  37. Yashiro M, Hirakawa K (2010) Cancer-stromal interactions in scirrhous gastric carcinoma. Cancer Microenviron 3:127ā€“135

    ArticleĀ  CASĀ  PubMedĀ  PubMed CentralĀ  Google ScholarĀ 

  38. Tang D, Gao J, Wang S, Ye N, Chong Y, Huang Y, Wang J, Li B, Yin W, Wang D (2016) Cancer-associated fibroblasts promote angiogenesis in gastric cancer through galectin-1 expression. Tumour Biol 37(2):1889ā€“1899

    ArticleĀ  CASĀ  PubMedĀ  Google ScholarĀ 

  39. Kwa MQ, Herum KM, Brakebusch C (2019) Cancer-associated fibroblasts: how do they contribute to metastasis? Clin Exp Metastasis. https://doi.org/10.1007/s10585-019-09959-0

    ArticleĀ  CASĀ  Google ScholarĀ 

  40. Mishra P, Banerjee D, Ben-Baruch A (2011) Chemokines at the crossroads of tumor-fibroblast interactions that promote malignancy. J Leukoc Biol 89(1):31ā€“39

    ArticleĀ  CASĀ  PubMedĀ  Google ScholarĀ 

  41. Wu X, Tao P, Zhou Q, Li J, Yu Z, Wang X, Li J, Li C, Yan M, Zhu Z, Liu B, Su L (2017) IL-6 secreted by cancer-associated fibroblasts promotes epithelial-mesenchymal transition and metastasis of gastric cancer via JAK2/STAT3 signaling pathway. Oncotarget 8(13):20741ā€“20750

    PubMedĀ  PubMed CentralĀ  Google ScholarĀ 

  42. Alkasalias T, Moyano-Galceran L, Arsenian-Henriksson M, Lehti K (2018) Fibroblasts in the tumor microenvironment: shield or spear? Int J Mol Sci 19(5):1532

    ArticleĀ  PubMed CentralĀ  CASĀ  Google ScholarĀ 

  43. Park SJ, Nakagawa T, Kitamura H, Atsumi T, Kamon H, Sawa S, Kamimura D, Ueda N, Iwakura Y, Ishihara K, Murakami M, Hirano T (2004) IL-6 regulates in vivo dendritic cell differentiation through STAT3 activation. J Immunol 173(6):3844ā€“3854

    ArticleĀ  CASĀ  PubMedĀ  Google ScholarĀ 

  44. Comito G, Giannoni E, Segura CP, Barcellos-de-Souza P, Raspollini MR, Baroni G, Lanciotti M, Serni S, Chiarugi P (2014) Cancer-associated fibroblasts and M2-polarized macrophages synergize during prostate carcinoma progression. Oncogene 33:2423ā€“2431

    ArticleĀ  CASĀ  PubMedĀ  Google ScholarĀ 

  45. Harper J, Sainson RC (2014) Regulation of the anti-tumor immune response by cancer-associated fibroblasts. Semin Cancer Biol 25:69ā€“77

    ArticleĀ  CASĀ  PubMedĀ  Google ScholarĀ 

  46. Mantovani A, Schioppa T, Porta C, Allavena P, Sica A (2006) Role of tumor-associated macrophages in tumor progression and invasion. Cancer Metastasis Rev 25:315ā€“322

    ArticleĀ  PubMedĀ  Google ScholarĀ 

  47. Solinas G, Germano G, Mantovani A, Allavena P (2009) Tumor-associated macrophages (TAM) as major players of the cancer-related inflammation. J Leukoc Biol 86:1065ā€“1073

    ArticleĀ  CASĀ  PubMedĀ  Google ScholarĀ 

  48. Prenen H, Mazzone M (2019) Tumor-associated macrophages: a short compendium. Cell Mol Life Sci. https://doi.org/10.1007/s00018-018-2997-3

    ArticleĀ  CASĀ  PubMedĀ  Google ScholarĀ 

  49. Pollard JW (2004) Tumor-educated macrophages promote tumor progression and metastasis. Nat Rev Cancer 4:71ā€“78

    ArticleĀ  CASĀ  PubMedĀ  Google ScholarĀ 

  50. Martinez FO, Gordon S, Locati M, Mantovani A (2006) Transcriptional profiling of the human monocyte-to-macrophage differentiation and polarization: new molecules and patterns of gene expression. J Immunol 177:7303ā€“7311

    ArticleĀ  CASĀ  PubMedĀ  Google ScholarĀ 

  51. Beyer M, Mallmann MR, Xue J, Staratschek-Jox A, Vorholt D, Krebs W, Sommer D, Sander J, Mertens C, Nino-Castro A, Schmidt SV, Schultze JL (2012) High-resolution transcriptome of human macrophages. PLoS One 7(9):e45466

    ArticleĀ  CASĀ  PubMedĀ  PubMed CentralĀ  Google ScholarĀ 

  52. Rojas A, Delgado-LĆ³pez F, Perez-Castro R, Gonzalez I, Romero J, Rojas I, Araya P, AƱazco C, Morales E, Llanos J (2016) HMGB1 enhances the protumoral activities of M2 macrophages by a RAGE-dependent mechanism. Tumour Biol 37(3):3321ā€“3329

    ArticleĀ  CASĀ  PubMedĀ  Google ScholarĀ 

  53. Rojas A, AƱazco C, Araya P (2017) M2 macrophages do not fly into a ā€œRAGEā€. Inflamm Res 66(1):13ā€“15

    ArticleĀ  CASĀ  PubMedĀ  Google ScholarĀ 

  54. Rojas A, Araya P, Romero J, Delgado-LĆ³pez F, Gonzalez I, AƱazco C, Perez-Castro R (2018) Skewed signaling through the receptor for advanced glycation end-products alters the proinflammatory profile of tumor-associated macrophages. Cancer Microenviron 11(2-3):97ā€“105

    ArticleĀ  CASĀ  PubMedĀ  PubMed CentralĀ  Google ScholarĀ 

  55. Ishigami S, Natsugoe S, Tokuda K, Nakajo A, Okumura H, Matsumoto M, Miyazono F, Hokita S, Aikou T (2003) Tumor-associated macrophage (TAM) infiltration in gastric cancer. Anticancer Res 23(5A):4079ā€“4083

    CASĀ  PubMedĀ  Google ScholarĀ 

  56. Wang XL, Jiang JT, Wu CP (2016) Prognostic significance of tumor-associated macrophage infiltration in gastric cancer: a meta-analysis. Genet Mol Res 15(4). https://doi.org/10.4238/gmr15049040

  57. Yan Y, Zhang J, Li JH, Liu X, Wang JZ, Qu HY, Wang JS, Duan XY (2016) High tumor-associated macrophages infiltration is associated with poor prognosis and may contribute to the phenomenon of epithelial-mesenchymal transition in gastric cancer. Onco Targets Ther 9:3975ā€“3983

    ArticleĀ  CASĀ  PubMedĀ  PubMed CentralĀ  Google ScholarĀ 

  58. RƤihƤ MR, Puolakkainen PA (2018) Tumor-associated macrophages (TAMs) as biomarkers for gastric cancer: a review. Chronic Dis Transl Med 4(3):156ā€“163

    ArticleĀ  PubMedĀ  PubMed CentralĀ  Google ScholarĀ 

  59. Houghton AM, Rzymkiewicz DM, Ji H, Gregory AD, Egea EE, Metz HE, Stolz DB, Land SR, Marconcini LA, Kliment CR, Jenkins KM, Beaulieu KA, Mouded M, Frank SJ, Wong KK, Shapiro SD (2010) Neutrophil elastase-mediated degradation of IRS-1 accelerates lung tumor growth. Nat Med 16(2):219ā€“223

    ArticleĀ  CASĀ  PubMedĀ  PubMed CentralĀ  Google ScholarĀ 

  60. Antonio N, Bonnelykke-Behrndtz ML, Ward LC, Collin J, Christensen IJ, Steiniche T, Schmidt H, Feng Y, Martin P (2015) The wound inflammatory response exacerbates growth of pre-neoplastic cells and progression to cancer. EMBO J 34(17):2219ā€“2236

    ArticleĀ  CASĀ  PubMedĀ  PubMed CentralĀ  Google ScholarĀ 

  61. Wculek SK, Malanchi I (2015) Neutrophils support lung colonization of metastasis-initiating breast cancer cells. Nature 528:413ā€“417

    ArticleĀ  CASĀ  PubMedĀ  PubMed CentralĀ  Google ScholarĀ 

  62. El Rayes T, Catena R, Lee S, Stawowczyk M, Joshi N, Fischbach C, Powell CA, Dannenberg AJ, Altorki NK, Gao D, Mittal V (2015) Lung inflammation promotes metastasis through neutrophil protease-mediated degradation of Tsp-1. Proc Natl Acad Sci U S A 112(52):16000ā€“16005

    ArticleĀ  PubMedĀ  PubMed CentralĀ  CASĀ  Google ScholarĀ 

  63. Casbon AJ, Reynaud D, Park C, Khuc E, Gan DD, Schepers K, PasseguĆ© E, Werb Z (2015) Invasive breast cancer reprograms early myeloid differentiation in the bone marrow to generate immunosuppressive neutrophils. Proc Natl Acad Sci U S A 112(6):E566ā€“E575

    ArticleĀ  CASĀ  PubMedĀ  PubMed CentralĀ  Google ScholarĀ 

  64. Zhou SL, Zhou ZJ, Hu ZQ, Huang XW, Wang Z, Chen EB, Fan J, Cao Y, Dai Z, Zhou J (2016) Tumor-associated neutrophils recruit macrophages and T-regulatory cells to promote progression of hepatocellular carcinoma and resistance to sorafenib. Gastroenterology 150(7):1646ā€“1658

    ArticleĀ  CASĀ  PubMedĀ  Google ScholarĀ 

  65. Fridlender ZG, Sun J, Kim S, Kapoor V, Cheng G, Ling L, Worthen GS, Albelda SM (2009) Polarization of tumor-associated neutrophil phenotype by TGF-beta: "N1" versus "N2" TAN. Cancer Cell 16(3):183ā€“194

    ArticleĀ  CASĀ  PubMedĀ  PubMed CentralĀ  Google ScholarĀ 

  66. Zhang W, Gu J, Chen J, Zhang P, Ji R, Qian H, Xu W, Zhang X (2017) Interaction with neutrophils promotes gastric cancer cell migration and invasion by inducing epithelial-mesenchymal transition. Oncol Rep 38(5):2959ā€“2966

    ArticleĀ  CASĀ  PubMedĀ  Google ScholarĀ 

  67. Jiang YX, Yang SW, Li PA, Luo X, Li ZY, Hao YX, Yu PW (2017) The promotion of the transformation of quiescent gastric cancer stem cells by IL-17 and the underlying mechanisms. Oncogene 36(9):1256ā€“1264

    ArticleĀ  CASĀ  PubMedĀ  Google ScholarĀ 

  68. Li S, Cong X, Gao H, Lan X, Li Z, Wang W, Song S, Wang Y, Li C, Zhang H, Xue Y, Zhao Y (2019) Tumor-associated neutrophils induce EMT by IL-17a to promote migration and invasion in gastric cancer cells. J Exp Clin Cancer Res 38(1):6

    ArticleĀ  PubMedĀ  PubMed CentralĀ  Google ScholarĀ 

  69. Wang TT, Zhao YL, Peng LS, , Chen N, Chen W, Li YP, Mao FY, Zhang JY, Cheng P, Teng YS, Fu XL, Yu PW, Guo G, Luo P, Zhuang Y, Zou QM (2017) Tumour-activated neutrophils in gastric cancer foster immune suppression and disease progression through GM-CSF-PD-L1 pathway. Gut; 66(11):1900ā€“1911. doi:https://doi.org/10.1136/gutjnl-2016-313075.

    ArticleĀ  CASĀ  PubMedĀ  Google ScholarĀ 

  70. Zhang H, Liu H, Shen Z, Lin C, Wang X, Qin J, Qin X, Xu J, Sun Y (2018) Tumor-infiltrating neutrophils are prognostic and predictive for postoperative adjuvant chemotherapy benefit in patients with gastric cancer. Ann Surg 267(2):311ā€“318

    ArticleĀ  PubMedĀ  Google ScholarĀ 

  71. Frantz C, Stewart KM, Weaver VM (2010) The extracellular matrix at a glance. J. Cell Sci 123:4195ā€“4200

    ArticleĀ  CASĀ  Google ScholarĀ 

  72. Lu P, Takai K, Weaver VM, Werb Z (2011) Extracellular matrix degradation and remodeling in development and disease. Cold Spring Harb Perspect Biol 3:1ā€“24

    ArticleĀ  Google ScholarĀ 

  73. Johansson N, Ahonen M, KƤhƤri VM (2000) Matrix metalloproteinases in tumor invasion. Cell Mol Life Sci 57(1):5ā€“15

    ArticleĀ  CASĀ  PubMedĀ  Google ScholarĀ 

  74. Kessenbrock K, Plaks V, Werb Z (2010) Matrix metalloproteinases: regulators of the tumor microenvironment. Cell 141(1):52ā€“67

    ArticleĀ  CASĀ  PubMedĀ  PubMed CentralĀ  Google ScholarĀ 

  75. Shim K, Jung S, Joo Y, Yoo K (2007) Clinical significance of tissue levels of matrix metalloproteinases and tissue inhibitors of metalloproteinases in gastric cancer. J Gastroenterol 42:120ā€“128

    ArticleĀ  CASĀ  PubMedĀ  Google ScholarĀ 

  76. Rojas A, AƱazco C, GonzĆ”lez I, Araya P (2018) Extracellular matrix glycation and receptor for advanced glycation end-products activation: a missing piece in the puzzle of the association between diabetes and cancer. Carcinogenesis 39(4):515ā€“521

    ArticleĀ  CASĀ  PubMedĀ  Google ScholarĀ 

  77. Łukaszewicz-Zając M, Szmitkowski M, Litman-Zawadzka A, Mroczko B (2016) Matrix metalloproteinases and their tissue inhibitors in comparison to other inflammatory proteins in gastric cancer (GC). Cancer Invest 34(7):305ā€“312

    ArticleĀ  PubMedĀ  CASĀ  Google ScholarĀ 

  78. Jang M, Koh I, Lee JE, Lim JY, Cheong JH, Kim P (2018) Increased extracellular matrix density disrupts E-cadherin/Ī²-catenin complex in gastric cancer cells. Biomater Sci 6(10):2704ā€“2713

    ArticleĀ  CASĀ  PubMedĀ  Google ScholarĀ 

  79. Chiurillo MA (2015) Role of the Wnt/Ī²-catenin pathway in gastric cancer: An in-depth literature review. World J Exp Med 5(2):84ā€“102

    ArticleĀ  PubMedĀ  PubMed CentralĀ  Google ScholarĀ 

  80. Yu H, Mouw JK, Weaver VM (2011) Forcing form and function: biomechanical regulation of tumor evolution. Trends Cell Biol 21(1):47ā€“56

    ArticleĀ  PubMedĀ  Google ScholarĀ 

  81. Levental KR, Yu H, Kass L, Lakins JN, Egeblad M, Erler JT, Fong SF, Csiszar K, Giaccia A, Weninger W, Yamauchi M, Gasser DL, Weaver VM (2009) Matrix crosslinking forces tumor progression by enhancing integrin signaling. Cell 139(5):891ā€“906

    ArticleĀ  CASĀ  PubMedĀ  PubMed CentralĀ  Google ScholarĀ 

  82. Xiao Q, Ge G (2012) Lysyl oxidase, extracellular matrix remodeling, and cancer metastasis. Cancer Microenviron 5(3):261ā€“273

    ArticleĀ  CASĀ  PubMedĀ  PubMed CentralĀ  Google ScholarĀ 

  83. Kasashima H, Yashiro M, Kinoshita H, Fukuoka T, Morisaki T, Masuda G, Sakurai K, Kubo N, Ohira M, Hirakawa K (2016) Lysyl oxidase is associated with the epithelial-mesenchymal transition of gastric cancer cells in hypoxia. Gastric Cancer 19(2):431ā€“442

    ArticleĀ  CASĀ  PubMedĀ  Google ScholarĀ 

  84. AƱazco C, Delgado-LĆ³pez F, Araya P, GonzĆ”lez I, Morales E, PĆ©rez-Castro R, Romero J, Rojas A (2016) Lysyl oxidase isoforms in gastric cancer. Biomark Med 10(9):987ā€“998

    ArticleĀ  PubMedĀ  CASĀ  Google ScholarĀ 

  85. Carthew RW, Sontheimer EJ (2009) Origins and mechanisms of miRNAs and siRNAs. Cell 136:642ā€“655

    ArticleĀ  CASĀ  PubMedĀ  PubMed CentralĀ  Google ScholarĀ 

  86. Suzuki HI, Katsura A, Matsuyama H, Miyazono K (2015) MicroRNA regulons in the tumor microenvironment. Oncogene 34(24):3085ā€“3094

    ArticleĀ  CASĀ  PubMedĀ  Google ScholarĀ 

  87. Yang L, Liang H, Wang Y, Gao S, Yin K, Liu Z, Zheng X, Li Y, Wang L, Zhang CY, Chen X, Xu G, Zhang W, Zou X (2016) Mi RNA-203 suppresses tumor cell proliferation, migration and invasion by targeting Slug in gastric cancer. Protein Cell 7(5):383ā€“387

    ArticleĀ  PubMedĀ  PubMed CentralĀ  Google ScholarĀ 

  88. Link A, Schirrmeister W, Langner C, Varbanova M, Bornschein J, Wex T, Malfertheiner P (2015) Differential expression of microRNAs in preneoplastic gastric mucosa. Sci Rep 5:8270

    ArticleĀ  CASĀ  PubMedĀ  PubMed CentralĀ  Google ScholarĀ 

  89. Huang T, Kang W, Zhang B, Wu F, Dong Y, Tong JH, Yang W, Zhou Y, Zhang L, Cheng AS, Yu J, To KF (2016) miR-508-3p concordantly silences NFKB1 and RELA to inactivate canonical NF-ĪŗB signaling in gastric carcinogenesis. Mol Cancer 15:9

    ArticleĀ  PubMedĀ  PubMed CentralĀ  CASĀ  Google ScholarĀ 

  90. Yanaka Y, Muramatsu T, Uetake H, Kozaki K, Inazawa J (2015) miR-544a induces epithelial-mesenchymal transition through the activation of WNT signaling pathway in gastric cancer. Carcinogenesis 36:1363ā€“1371

    ArticleĀ  CASĀ  PubMedĀ  Google ScholarĀ 

  91. Chen S, Wu J, Jiao K, Wu Q, Ma J, Chen D, Kang J, Zhao G, Shi Y, Fan D, Zhao G (2018) microRNA-495-3p inhibits multidrug resistance by modulating autophagy through GRP78/mTOR axis in gastric cancer. Cell Death Dis 9(11):1070

    ArticleĀ  PubMedĀ  PubMed CentralĀ  CASĀ  Google ScholarĀ 

  92. Cao Y, Luo Y, Zou J, Ouyang J, Cai Z, Zeng X, Ling H, Zeng T (2019) Autophagy and its role in gastric cancer. Clin Chim Acta 489:10ā€“20

    ArticleĀ  CASĀ  PubMedĀ  Google ScholarĀ 

  93. Johnstone RM (1992) The Jeanne Manery-Fisher Memorial Lecture 1991. Maturation of reticulocytes: formation of exosomes as a mechanism for shedding membrane proteins. Biochem Cell Biol 70(3-4):179ā€“190

    ArticleĀ  CASĀ  PubMedĀ  Google ScholarĀ 

  94. Vlassov AV, Magdaleno S, Setterquist R (2012) Exosomes: current knowledge of their composition, biological functions, and diagnostic and therapeutic potentials. Biochim Biophys Acta 1820(7):940ā€“948

    ArticleĀ  CASĀ  PubMedĀ  Google ScholarĀ 

  95. Qu JL, Qu XJ, Zhao MF, Teng YE, Zhang Y, Hou KZ, Jiang YH, Yang XH, Liu YP (2009) Gastric cancer exosomes promote tumor cell proliferation through PI3K/Akt and MAPK/ERK activation. Dig Liver Dis 41(12):875ā€“880

    ArticleĀ  CASĀ  PubMedĀ  Google ScholarĀ 

  96. Fu M, Gu J, Jiang P, Qian H, Xu W, Zhang X (2019) Exosomes in gastric cancer: roles, mechanisms, and applications. Mol Cancer 18(1):41

    ArticleĀ  PubMedĀ  PubMed CentralĀ  Google ScholarĀ 

  97. Kahroba H, Hejazi MS, Samadi N (2019) Exosomes: from carcinogenesis and metastasis to diagnosis and treatment of gastric cancer. Cell Mol Life Sci. https://doi.org/10.1007/s00018-019-03035-2

    ArticleĀ  CASĀ  PubMedĀ  Google ScholarĀ 

  98. Thomassen I, van Gestel YR, van Ramshorst B, Luyer MD, Bosscha K, Nienhuijs SW, Lemmens VE, de Hingh IH (2014) Peritoneal carcinomatosis of gastric origin: a population-based study on incidence, survival and risk factors. Int J Cancer 134(3):622ā€“628

    ArticleĀ  CASĀ  PubMedĀ  Google ScholarĀ 

  99. Chen KB, Chen J, Jin XL, Huang Y, Su QM, Chen L (2018) Exosome-mediated peritoneal dissemination in gastric cancer and its clinical applications. Biomed Rep 8(6):503ā€“509

    CASĀ  PubMedĀ  PubMed CentralĀ  Google ScholarĀ 

  100. Aung T, Chapuy B, Vogel D, Wenzel D, Oppermann M, Lahmann M, Weinhage T, Menck K, Hupfeld T, Koch R, TrĆ¼mper L, Wulf GG (2011) Exosomal evasion of humoral immunotherapy in aggressive B-cell lymphoma modulated by ATP-binding cassette transporter A3. Proc Natl Acad Sci U S A 108(37):15336ā€“15341

    ArticleĀ  CASĀ  PubMedĀ  PubMed CentralĀ  Google ScholarĀ 

  101. Shedden K, Xie XT, Chandaroy P, Chang YT, Rosania GR (2003) Expulsion of small molecules in vesicles shed by cancer cells: association with gene expression and chemosensitivity profiles. Cancer Res 63(15):4331ā€“4337

    CASĀ  PubMedĀ  Google ScholarĀ 

  102. Liu F, Bu Z, Zhao F, Xiao D (2018) Increased T-helper 17 cell differentiation mediated by exosome-mediated microRNA-451 redistribution in gastric cancer infiltrated T cells. Cancer Sci 109:65ā€“73

    ArticleĀ  CASĀ  PubMedĀ  Google ScholarĀ 

  103. Shen Y, Xue C, Li X, Ba L, Gu J, Sun Z, Han Q, Zhao RC (2019) Effects of gastric cancer cell-derived exosomes on the immune regulation of mesenchymal stem cells by the nf-kb signaling pathway. Stem Cells Dev 28(7):464ā€“476

    ArticleĀ  CASĀ  PubMedĀ  Google ScholarĀ 

  104. Houghton J, Wang TC (2005) Helicobacter pylori and gastric cancer: a new paradigm for inflammation-associated epithelial cancers. Gastroenterology 128(6):1567ā€“1578

    ArticleĀ  CASĀ  PubMedĀ  Google ScholarĀ 

  105. Kumari S, Puneet PSB, Yadav SS, Kumar M, Khanna A, Dixit VK, Nath G, Singh S, Narayan G (2016) Cyclin D1 and cyclin E2 are differentially expressed in gastric cancer. Med Oncol 33(5):40

    ArticleĀ  PubMedĀ  CASĀ  Google ScholarĀ 

  106. Sasaki N, Morisaki T, Hashizume K, Yao T, Tsuneyoshi M, Noshiro H, Nakamura K, Yamanaka T, Uchiyama A, Tanaka M, Katano M (2001) Nuclear factor-kappaB p65 (RelA) transcription factor is constitutively activated in human gastric carcinoma tissue. Clin Cancer Res 7(12):4136ā€“4142

    CASĀ  PubMedĀ  Google ScholarĀ 

  107. Yamaoka Y, Kudo T, Lu H, Casola A, Brasier AR, Graham DY (2004) Role of the interferon-stimulated responsive element-like element in interleukin-8 promoter in Helicobacter pylori infection. Gastroenterology 126:1030ā€“1043

    ArticleĀ  CASĀ  PubMedĀ  Google ScholarĀ 

  108. Pachathundikandi SK, MĆ¼ller A, Backert S (2016) Inflammasome activation by Helicobacter pylori and its implications for persistence and immunity. Curr Top Microbiol Immunol 397:117ā€“131

    CASĀ  PubMedĀ  Google ScholarĀ 

  109. Hu Y, Liu JP, Zhu Y, Lu NH (2016) The importance of toll-like receptors in nf-Īŗb signaling pathway activation by Helicobacter pylori infection and the regulators of this response. Helicobacter 21(5):428ā€“440

    ArticleĀ  CASĀ  PubMedĀ  Google ScholarĀ 

  110. Rojas A, GonzĆ”lez I, RodrĆ­guez B, Romero J, Figueroa H, Llanos J, Morales E, PĆ©rez-Castro R (2011) Evidence of involvement of the receptor for advanced glycation end-products (RAGE) in the adhesion of Helicobacter pylori to gastric epithelial cells. Microbes Infect 13(10):818ā€“823

    ArticleĀ  CASĀ  PubMedĀ  Google ScholarĀ 

  111. Yeh TS, Wu CW, Hsu KW, Liao WJ, Yang MC, Li AF, Wang AM, Kuo ML, Chi CW (2009) The activated Notch1 signal pathway is associated with gastric cancer progression through cyclooxygenase-2. Cancer Res 69(12):5039ā€“5048

    ArticleĀ  CASĀ  PubMedĀ  Google ScholarĀ 

  112. Xiao C, Ogle SA, Schumacher MA, Orr-Asman MA, Miller ML, Lertkowit N, Varro A, Hollande F, Zavros Y (2010) Loss of parietal cell expression of sonic hedgehog induces hypergastrinemia and hyperproliferation of surface mucous cells. Gastroenterology 138:550ā€“556

    ArticleĀ  CASĀ  PubMedĀ  Google ScholarĀ 

  113. Lee SY, Han HS, Lee KY, Hwang TS, Kim JH, Sung IK, Park HS, Jin CJ, Choi KW (2007) Sonic hedgehog expression in gastric cancer and gastric adenoma. Oncol Rep 17(5):1051ā€“1055

    PubMedĀ  Google ScholarĀ 

  114. Wang LH, Choi YL, Hua XY, Shin YK, Song YJ, Youn SJ, Yun HY, Park SM, Kim WJ, Kim HJ, Choi JS, Kim SH (2006) Increased expression of sonic hedgehog and altered methylation of its promoter region in gastric cancer and its related lesions. Mod Pathol 19(5):675ā€“683

    ArticleĀ  CASĀ  PubMedĀ  Google ScholarĀ 

  115. Schumacher MA, Feng R, Aihara E, Engevik AC, Montrose MH, Ottemann KM, Zavros Y (2015) Helicobacter pylori-induced Sonic Hedgehog expression is regulated by NFĪŗB pathway activation: the use of a novel in vitro model to study epithelial response to infection. Helicobacter 20(1):19ā€“28

    ArticleĀ  CASĀ  PubMedĀ  Google ScholarĀ 

  116. Clevers H (2006) Wnt/beta-catenin signaling in development and disease. Cell 127(3):469ā€“480

    ArticleĀ  CASĀ  PubMedĀ  Google ScholarĀ 

  117. Cai C, Zhu X (2012) The Wnt/Ī²-catenin pathway regulates self-renewal of cancer stem-like cells in human gastric cancer. Mol Med Rep 5:1191ā€“1196

    CASĀ  PubMedĀ  Google ScholarĀ 

  118. Hanaki H, Yamamoto H, Sakane H, Matsumoto S, Ohdan H, Sato A, Kikuchi A (2012) An anti-Wnt5a antibody suppresses metastasis of gastric cancer cells in vivo by inhibiting receptor-mediated endocytosis. Mol Cancer Ther 11(2):298ā€“307

    ArticleĀ  CASĀ  PubMedĀ  Google ScholarĀ 

  119. Song X, Xin N, Wang W, Zhao C (2015) Wnt/Ī²-catenin, an oncogenic pathway targeted by H. pylori in gastric carcinogenesis. Oncotarget 6(34):35579ā€“35588

    ArticleĀ  PubMedĀ  PubMed CentralĀ  Google ScholarĀ 

  120. Zhou GX, Li XY, Zhang Q, Zhao K, Zhang CP, Xue CH, Yang K, Tian ZB (2013) Effects of the Hippo signaling pathway in human gastric cancer. Asian Pac J Cancer Prev 14(9):5199ā€“5205

    ArticleĀ  PubMedĀ  Google ScholarĀ 

  121. Varelas X, Miller BW, Sopko R, Song S, Gregorieff A, Fellouse FA, Sakuma R, Pawson T, Hunziker W, McNeill H, Wrana JL, Attisano L (2010) The Hippo pathway regulates Wnt/beta-catenin signaling. Dev Cell 18(4):579ā€“591

    ArticleĀ  CASĀ  PubMedĀ  Google ScholarĀ 

  122. Chen HJ, Wang CM, Wang TW, Liaw GJ, Hsu TH, Lin TH, Yu JY (2011) The Hippo pathway controls polar cell fate through Notch signaling during Drosophila oogenesis. Dev Biol 357(2):370ā€“379

    ArticleĀ  CASĀ  PubMedĀ  Google ScholarĀ 

  123. Fujii M, Toyoda T, Nakanishi H, Yatabe Y, Sato A, Matsudaira Y, Ito H, Murakami H, Kondo Y, Kondo E, Hida T, Tsujimura T, Osada H, Sekido Y (2012) TGF-Ī² synergizes with defects in the Hippo pathway to stimulate human malignant mesothelioma growth. J Exp Med 209(3):479ā€“494

    ArticleĀ  CASĀ  PubMedĀ  PubMed CentralĀ  Google ScholarĀ 

  124. Katz LH, Li Y, Chen JS, MuƱoz NM, Majumdar A, Chen J, Mishra L (2013) Targeting TGF-Ī² signaling in cancer. Expert Opin Ther Targets 17(7):743ā€“760

    ArticleĀ  CASĀ  PubMedĀ  PubMed CentralĀ  Google ScholarĀ 

  125. David CJ, Massague J (2018) Contextual determinants of TGF-beta action in development, immunity, and cancer. Nat Rev Mol Cell Biol 19(7):419ā€“435

    ArticleĀ  CASĀ  PubMedĀ  PubMed CentralĀ  Google ScholarĀ 

  126. Leng A, Liu T, He Y, Li Q, Zhang G (2009) Smad4/Smad7 balance: a role of tumorigenesis in gastric cancer. Exp Mol Pathol 87(1):48ā€“53

    ArticleĀ  CASĀ  PubMedĀ  Google ScholarĀ 

  127. Ma H, Gao L, Li S, Qin J, Chen L, Liu X, Xu P, Wang F, Xiao H, Zhou S (2015) CCR7 enhances TGF-beta1-induced epithelial-mesenchymal transition and is associated with lymph node metastasis and poor overall survival in gastric cancer. Oncotarget 6(27):24348ā€“24360

    ArticleĀ  PubMedĀ  PubMed CentralĀ  Google ScholarĀ 

  128. Ouyang S, Zhu G, Ouyang L, Luo Y, Zhou R, Pan C, Bin J, Liao Y, Liao W (2017) Bapx1 mediates transforming growth factor-beta-induced epithelial-mesenchymal transition and promotes a malignancy phenotype of gastric cancer cells. Biochem Biophys Res Commun 486(2):285ā€“292

    ArticleĀ  CASĀ  PubMedĀ  Google ScholarĀ 

  129. Wieduwilt MJ, Moasser MM (2008) The epidermal growth factor receptor family: biology driving targeted therapeutics. Cell Mol Life Sci 65(10):1566ā€“1584

    ArticleĀ  CASĀ  PubMedĀ  PubMed CentralĀ  Google ScholarĀ 

  130. Holbro T, Hynes NE (2004) ErbB receptors: directing key signaling networks throughout life. Annu Rev Pharmacol Toxicol 44:195ā€“217

    ArticleĀ  CASĀ  PubMedĀ  Google ScholarĀ 

  131. Abhold EL, Kiang A, Rahimy E, Kuo SZ, Wang-Rodriguez J, Lopez JP, Blair KJ, Yu MA, Haas M, Brumund KT, Altuna X, Patel A, Weisman RA, Ongkeko WM (2012) EGFR kinase promotes acquisition of stem cell-like properties: a potential therapeutic target in head and neck squamous cell carcinoma stem cells. PLoS One 7(2):e32459

    ArticleĀ  CASĀ  PubMedĀ  PubMed CentralĀ  Google ScholarĀ 

  132. Kim SJ, Uehara H, Karashima T, Shepherd DL, Killion JJ, Fidler IJ (2003) Blockade of epidermal growth factor receptor signaling in tumor cells and tumor-associated endothelial cells for therapy of androgen-independent human prostate cancer growth in the bone of nude mice. Clin Cancer Res 9:1200ā€“1210

    CASĀ  PubMedĀ  Google ScholarĀ 

  133. Takahashi M, Nakajima M, Ogata H, Domeki Y, Ohtsuka K, Ihara K, Kurayama E, Yamaguchi S, Sasaki K, Miyachi K, Kato H (2013) CD24 expression is associated with progression of gastric cancer. Hepatogastroenterology 60:653ā€“658

    CASĀ  PubMedĀ  Google ScholarĀ 

  134. Wang YC, Wang JL, Kong X, Sun TT, Chen HY, Hong J, Fang JY (2014) CD24 mediates gastric carcinogenesis and promotes gastric cancer progression via STAT3 activation. Apoptosis 19:643ā€“656. https://doi.org/10.1007/s10495-013-0949-9.c

    ArticleĀ  CASĀ  PubMedĀ  Google ScholarĀ 

  135. Chou YY, Jeng YM, Lee TT, Hu FC, Kao HL, Lin WC, Lai PL, Hu RH, Yuan RH (2007) Cytoplasmic CD24 expression is a novel prognostic factor in diffuse-type gastric adenocarcinoma. Ann Surg Oncol 14(10):2748ā€“2758

    ArticleĀ  PubMedĀ  Google ScholarĀ 

  136. Deng W, Gu L, Li X, Zheng J, Zhang Y, Duan B, Cui J, Dong J, Du J (2016) CD24 associates with EGFR and supports EGF/EGFR signaling via RhoA in gastric cancer cells. J Transl Med 14:32

    ArticleĀ  PubMedĀ  PubMed CentralĀ  CASĀ  Google ScholarĀ 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Armando Rojas .

Editor information

Editors and Affiliations

Rights and permissions

Reprints and permissions

Copyright information

Ā© 2020 Springer Nature Switzerland AG

About this chapter

Check for updates. Verify currency and authenticity via CrossMark

Cite this chapter

Rojas, A., Araya, P., Gonzalez, I., Morales, E. (2020). Gastric Tumor Microenvironment. In: Birbrair, A. (eds) Tumor Microenvironments in Organs. Advances in Experimental Medicine and Biology, vol 1226. Springer, Cham. https://doi.org/10.1007/978-3-030-36214-0_2

Download citation

Publish with us

Policies and ethics