Abstract

The second half of the 20th century has seen a sharp worldwide decline in both the incidence and mortality of gastric cancer. Despite this, gastric cancer is the most common cause of mortality in the world. It is closely related to the commonly asymptomatic course at the beginning and delayed diagnosis. Approximately 90‑97% of stomach cancers are adenocarcinomas, which may be subdivided histologically into two categories – intestinal type, and diffuse type. Cancer metastasis is a complex multi‑step process that is closely associated with tumor phenotype. The most important steps in the metastasis process are proteolytic activity, migration, adhesion, proliferation, and neovascularization. In this review we focus on mechanisms regulating gastric cancer metastasis.

References

• 1. Amemiya H., Kono K., Itakura J., Tang r.F., Takahashi A., An F.Q.,Kamei S., Iizuka H., Fujii H., Matsumoto Y.: c‑Met expression in gastriccancer with liver metastasis. Oncology, 2002; 63: 286‑296
  Google Scholar
• 2. Anbiaee r., Mojir Sheibani K., Torbati P., Jaam H.: Abnormal expressionof E‑cadherin in gastric adenocarcinoma, and its correlationwith tumor histopathology and Helicobacter pylori infection.Iran. Red Crescent Med. J., 2013; 15: 218‑222
  Google Scholar
• 3. Bevan S., Houlston r.S.: Genetic predisposition to gastric cancer.Q. J. Med., 1999; 92: 5‑10
  Google Scholar
• 4. Bray F., Ren J.S., Masuyer E., Ferlay J.: Global estimates of cancerprevalence for 27 sites in the adult population in 2008. Int. J. Cancer,2013; 132: 1133‑1145
  Google Scholar
• 5. Castella E.M., Ariza A., Pellicer I., Fernandez‑Vasalo A., OjangurenI.: Differential expression of CD44v6 in metastases of intestinal anddiffuse types of gastric carcinoma. J. Clin. Pathol., 1998; 51: 134‑137
  Google Scholar
• 6. Chaffer C.L., Weinberg r.A.: A perspective on cancer cell metastasis.Science, 2011; 331: 1559‑1564
  Google Scholar
• 7. Dämmrich J., Vollmers H.P., Heider K.H., Müeller‑Hermelink H.K.:Importance of different CD44v6 expression in human gastric intestinaland diffuse type cancers for metastatic lymphogenic spreading.J. Mol. Med., 1995; 73: 395‑401
  Google Scholar
• 8. Deng B., Zhu J.M., Wang Y., Liu T.T., Ding Y.B., Xiao W.M., Lu G.T.,Bo P., Shen X.Z.: Intratumor hypoxia promotes immune tolerancePiśmiennictwoby inducing regulatory T cells via TGF‑β1 in gastric cancer. PLoSOne, 2013; 8:e63777
  Google Scholar
• 9. Eroğlu A., Demirci S., Ayyildiz A., Kocaoğlu H., Akbulut H., AkgülH., Elhan H.A.: Serum concentrations of vascular endothelial growthfactor and nitrite as an estimate of in vivo nitric oxide in patientswith gastric cancer. Br. J. Cancer, 1999; 80: 1630‑1634
  Google Scholar
• 10. Fitzgerald r.C., Hardwick r., Huntsman D., Carneiro F., GuilfordP., Blair V., Chung D.C, Norton J., Ragunath K., Van Krieken J.H., DwerryhouseS., Caldas C.: Hereditary diffuse gastric cancer: updateconsensus guidelines for clinical management and directions forfuture research. J. Med. Genet., 2010; 47: 436‑444
  Google Scholar
• 11. Forones N.M., Carvalho A.P., Giannotti‑Filho O., Lourenço L.G.,Oshima C.T.: Cell proliferation and apoptosis in gastric cancer andintestinal metaplasia. Arq. Gastroenterol., 2005; 42:30‑34
  Google Scholar
• 12. Frejlich E., Rudno‑Rudzińska J., Janiszewski K., Salomon Ł.,Kotulski K., Pelzer O., Grzebieniak Z., Tarnawa r., Kielan W.: Caspasesand their role in gastric cancer. Adv. Clin. Exp. Med., 2013; 22: 593‑602
  Google Scholar
• 13. Gieryng A., Bogunia‑Kubik K: Znaczenie interakcji między SDF‑1i CXCR4 w hematopoezie i mobilizacji macierzystych komórek hematopoetycznychdo krwi obwodowej. Postępy Hig. Med. Dośw.,2007; 61: 369‑383
  Google Scholar
• 14. Glinskii O.V., Huxley V.H., Glinsky G.V., Pienta K.J., Raz A., GlinskyV.V.: Mechanical entrapment is insufficient and intercellularadhesion is essential for metastatic cell arrest in distant organs. Neoplasia, 2005; 7: 522‑527
  Google Scholar
• 15. González C.A., Sala N., Rokkas T.: Gastric cancer: epidemiologicaspects. Helicobacter, 2013; 18, Suppl. 1: 34‑38
  Google Scholar
• 16. Hess K.R., Varadhachary G.R., Taylor S.H., Wei W., Raber M.N.,Lenzi r., Abbruzzese J.L.: Metastatic patterns in adenocarcinoma.Cancer, 2006; 106: 1624‑1633
  Google Scholar
• 17. Holash J., Wiegand S.J., Yancopoulos G.D.: New model of tumorangiogenesis: dynamic balance between vessels regression andgrowth mediated by angiopoietins and VEGF. Oncogene, 1999; 18:5356‑5362
  Google Scholar
• 18. Ichikawa J., Matsumoto S., Shimoji T., Tanizawa T., Gokita T., HayakawaK., Aoki K., Ina S., Kanda H.: Intraneural metastasis of gastriccarcinoma leads to sciatic nerve palsy. BMC Cancer, 2012; 12: 313
  Google Scholar
• 19. Iwasa S., Yanagawa T., Fan J., Katoh r.: Expression of CXCR4 andits ligand SDF‑1 in intestinal–type gastric cancer is associated withlymph node and liver metastasis. Anticancer Res., 2009; 29: 4751‑4758
  Google Scholar
• 20. Ji r.C.: Hypoxia and lymphangiogenesis in tumor microenvironmentand metastasis. Cancer Lett., 2014; 346: 6‑16
  Google Scholar
• 21. Jian P., Yanfang T., Zhuan Z., Jian W., Xueming Z., Jian N.: MMP28(epilysin) as a novel promoter of invasion and metastasis in gastriccancer. BMC Cancer, 2011; 11: 200
  Google Scholar
• 22. Jung W.C., Jang Y.J., Kim J.H., Park S.S., Park S.H., Kim S.J., MokY.J., Kim C.S.: Expression of intercellular adhesion molecule‑1 andE–selectin in gastric cancer and their clinical significance. J. GastricCancer, 2012; 12: 140‑148
  Google Scholar
• 23. Kakeji Y., Maehara Y., Sumiyoshi Y., Oda S., Emi Y.: Angiogenesisas a target for gastric cancer. Surgery, 2002; 131: S48‑S54
  Google Scholar
• 24. Karayiannakis A.J., Syrgios K.N., Polychronidis A., Zbar A.,Kouraklis G., Simopoulos C., Karatzas G.: Circulating VEGF levels inithe serum of gastric cancer patients: correlation with pathologicalvariables, patient survival, and tumor surgery. Ann. Surgery, 2002;236: 37‑42
  Google Scholar
• 25. Kelley J.R., Duggan J.M.: Gastric cancer epidemiology and riskfactors. J. Clin. Epidemiol., 2003; 56: 1‑9
  Google Scholar
• 26. Kitadai Y.: Cancer‑stromal cell interaction and tumor angiogenesisin gastric cancer. Cancer Microenviron., 2010; 3: 109‑116
  Google Scholar
• 27. Kitadai Y., Takahashi Y., Haruma K., Naka K., Sumii K., YokozakiH., Yasui W., Mukaida N., Ohmoto Y., Kajiyama G., Fidler I.J., TaharaE.: Transfection of interleukin‑8 increases angiogenesis and tumorigenesisof human gastric carcinoma cells in nude mice. Br. J. Cancer,1999; 81: 647‑653
  Google Scholar
• 28. Krajewska M., Kim H., Shin E., Kennedy S., Duffy M.J., Wong Y.F.,Marr D., Mikolajczyk J., Shabaik A., Meinhold‑Heerlein I., Huang X.,Banares S., Hedayat H., Reed J.C., Krajewski S.: Tumor‑associated alterationsin caspase‑14 expression in epithelial malignancies. Clin.Cancer Res., 2005; 11: 5462‑5471
  Google Scholar
• 29. Krzakowski M., Kawecki A.: Rak żołądka. W: Nowotwory złośliwe.Postępowanie wielodyscyplinarne. Leczenie systemowe, chirurgia,radioterapia, t. 2, red. C.D. Blanke, D. Citrin., r.E. Schwarz, WydawnictwoCzelej, Lublin 2012, 189‑198
  Google Scholar
• 30. Kwiatkowski P., Godlewski J., Śliwińska‑Jewsiewicka A., Kmieć Z.:Cząsteczki adhezyjne w procesie nowotworzenia i przerzutowania.Pol. Ann. Med., 2009; 16: 128‑137
  Google Scholar
• 31. Lazăr D., Tăban S., Sporea I., Dema A., Cornianu M., Lazăr E.,Goldis A., Vernic C.: Ki‑67 expression in gastric cancer. Results froma prospective study with long‑term follow up. Rom. J. Morphol. Embryol.,2010; 51: 655‑661
  Google Scholar
• 32. Lee H.J., Kim S.W., Kim H.Y., Li S., Yun H.J., Song K.S., Kim S., JoD.Y.: Chemokine receptor CXCR4 expression, function, and clinicalimplications in gastric cancer. Int. J. Oncol., 2009; 34: 473‑480
  Google Scholar
• 33. Lee H.J., Lee K.S., Ryu H., Song I.C., Huang S.M., Yun H.J., KimJ., Jo D.Y., Kim S.: The combined expression of CXCR7 and its ligandCXCL12 is a marker for unfavorable prognosis in gastric cancer. Ann.Oncol., 2012; 23, Suppl. 9: ix541‑ix545
  Google Scholar
• 34. Lin W., Kao H.W., Robinson D., Kung H.J., Wu C.W., Chen H.C.:Tyrosine kinases and gastric cancer. Oncogene, 2000; 19: 5680‑5689
  Google Scholar
• 35. Liu S.I., Lui W.Y., Mok K.T., Wu C.W., Chi C.W.: Effect of hepatocytegrowth factor on cell cycle and c–met expression in human gastriccancer cells. Anticancer Res., 1997; 17: 3575‑3580
  Google Scholar
• 36. Łapka A., Goździalska A., Jaśkiewicz J.: Rola metaloproteinaz macierzyzewnątrzkomórkowej w nowotworach piersi, ze szczególnymuwzględnieniem roli żelatynazy A oraz żelatynazy B. Postępy Biol.Kom., 2006; 33: 683‑695
  Google Scholar
• 37. Łukaszewicz‑Zając M., Mroczko B., Szmitkowski M.: Gastric cancer– the role of matrix metalloproteinases in tumor progression.Clin. Chim. Acta, 2011; 412: 1725‑1730
  Google Scholar
• 38. Maga G., Hübsher U.: Proliferating cell nuclear antigen (PCNA):a dancer with many partners. J. Cell Sci., 2003; 116: 3051‑3060
  Google Scholar
• 39. Marrelli D., Pedrazzani C., Berardi A., Corso G., Neri A., Garosi L.,Vindigni C., Santucci A., Figura N., Roviello F.: Negative Helicobacterpylori status is associated with poor prognosis in patients with gastriccancer. Cancer, 2009; 115: 2071‑2080
  Google Scholar
• 40. Meimarakis G., Winter H., Assmann I., Kopp r., Lehn N., Kist M.,Stolte M., Jauch K.W., Hatz r.A.: Helicobacter pylori as a prognostic indicatorafter curative resection of gastric carcinoma: a prospectivestudy. Lancet Oncol., 2006; 7: 211‑222
  Google Scholar
• 41. Moreira I.S., Fernandes P.A., Ramos M.J.: Vascular endothelialgrowth factor (VEGF) inhibition – a critical reviev. Anti‑CancerAgents Med. Chem., 2007; 7: 223‑245
  Google Scholar
• 42. Nam S.Y., Ko Y.S., Jung J., Yoon J., Kim Y.H., Choi Y.J., Park J.W.,Chang M.S., Kim W.H., Lee B.L.: A hypoxia‑dependent upregulationof hypoxia‑inducible factor‑1 by nuclear factor‑κB promotes gastrictumor growth and angiogenesis. Br. J. Cancer, 2011; 104: 166‑174
  Google Scholar
• 43. Oh S.Y., Kwon H.C., Kim S.H., Jang J.S., Kim M.C., Kim K.H., HanJ.Y., Kim C.O., Kim S.J., Jeong J.S., Kim H.J.: Clinicopathologic significanceof HIF‑1α, p53, and VEGF expression and preoperative serumVEGF level in gastric cancer. BMC Cancer, 2008; 8: 123
  Google Scholar
• 44. Olakowski M.: Rola czynników wzrostu w patogenezie rakatrzustki. Część III: Czynnik wzrostu śródbłonka naczyń krwiono-śnych (VEGF) i insulinopodobne czynniki wzrostu (IGFs). Prz. Gastroenterol.,2007; 2: 181‑184
  Google Scholar
• 45. Oliveira C., Seruca r., Carneiro F.: Hereditary gastric cancer. BestPract. Res. Clin. Gastroenterol., 2009; 23: 147‑157
  Google Scholar
• 46. Ozmen F., Ozmen M.M., Ozdemir E., Moran M.,Seçkin S., Guc D.,Karaagaoglu E., Kansu E.: Relationship between LYVE‑1, VEGFR‑3 andCD44 gene expressions and lymphatic metastasis in gastric cancer.World J. Gastroenterol., 2011; 17: 3220‑3228
  Google Scholar
• 47. Ren Y., Cao B., Law S., Xie Y., Lee P.Y., Cheung L., Chen Y., HuangX., Chan H.M., Zhao P., Luk J., Vande Woude G., Wong J: Hepatocytegrowth factor promotes cancer cell migration and angiogenic factorsexpression: a prognostic marker for human esophageal squamouscell carcinomas. Clin. Cancer Res., 2005; 11: 6190‑6197
  Google Scholar
• 48. Robles Campos r., Pinero Madrona A., Torralba Martínez J.A.,Parrilla Paricio P.: Gastric adenocarcinoma in 2 cases of Bloom syndrome.Med. Clin., 1996; 106: 156‑157
  Google Scholar
• 49. Rohwer N., Lobitz S., Daskalow K., Jöns T., Vieth M., Schlag P.M.,Kemmner W., Wiedenmann B., Cramer T., Höcker M.: HIF‑1α determinesthe metastatic potential of gastric cancer cells. Br. J. Cancer,2009;100: 772‑781
  Google Scholar
• 50. Roukos D.H., Agnantis N.J., Fatouros M., Kappas A.M.: Gastriccancer: introduction, pathology, epidemiology. Gastric Breast Cancer,2002; 1: 1‑3
  Google Scholar
• 51. Sceneay J., Smyth M.J., Möller A.: The pre‑metastatic niche:finding common ground. Cancer Metastasis Rev., 2013; 32: 449‑464
  Google Scholar
• 52. Seo H.Y., Park J.M., Park K.H., Kim S.J., Oh S.C., Kim B.S., KimY.H., Kim J.S.: Prognostic significance of serum vascular endothelialgrowth factor per platelet count in unresectable advanced gastriccancer patients. Jpn. J. Clin. Oncol., 2010; 40: 1147‑1153
  Google Scholar
• 53. Smith M.G., Hold G.L., Tahara E., El‑Omar E.M.: Cellular andmolecular aspects of gastric cancer. World J. Gastroenterol., 2006;12: 2979‑2990
  Google Scholar
• 54. Smolewski P., Grzybowska O.: Regulacja procesu apoptozy w celachterapeutycznych – dotychczasowe doświadczenia i perspektywyrozwoju. Acta. Haematol. Pol., 2002; 33: 393‑401
  Google Scholar
• 55. Stoeltzing O., McCarty M.F., Wey J.S., Fan F., Liu W., BelchevaA., Bucana C.D., Semenza G.L., Ellis L.M.: Role of hypoxia‑induciblefactor‑1α in gastric cancer cell growth, angiogenesis and vessel maturation.J. Natl. Cancer Inst., 2004; 96: 946‑956
  Google Scholar
• 56. Szala S.: Komórki mikrośrodowiska nowotworowego: cel terapiiprzeciwnowotworowej. Nowotwory, 2007; 57: 633‑645
  Google Scholar
• 57. Szczeklik A.: Nowotwory żołądka i dwunastnicy. W: Chorobywewnętrzne, t.1, red.: Marlicz K. Medycyna Praktyczna, Kraków2005, 786‑788
  Google Scholar
• 58. Tachezy M., Zander H., Gebauer F., von Loga K., Pantel K., IzbickiJ.R., Bockhorn M.: CXCR7 expression in esophageal cancer. J. Transl.Med., 2013; 11: 238
  Google Scholar
• 59. Tahara E.: Abnormal growth factor/cytokine network in gastriccancer. Cancer Microenviron., 2008; 1: 85‑91
  Google Scholar
• 60. Tanigawa N., Amaya H., Matsumura M., Shimomatsuya T., HoriuchiT., Muraoka r., Iki M.: Extent of tumor vascularization correlateswith prognosis and hematogenous metastasis in gastric carcinomas.Cancer Res., 1996; 56: 2671‑2676
  Google Scholar
• 61. Taniguchi T., Kitamura M., Arai K., Iwasaki Y., Yamamoto Y., IgariA., Toi M.: Increase in the circulating level of hepatocyte growthfactor in gastric cancer patients. Br. J. Cancer, 1997; 75: 673‑677
  Google Scholar
• 62. Tarnowski M., Grymuła K., Tkacz M., Czerewaty M., Poniewierska‑BaranA., Ratajczak M.Z.: Molekularne mechanizmy regulacjiprzerzutowania komórek nowotworowych na przykładzie mięsakaprążkowanokomórkowego (rhabdomyosarcoma). Postępy Hig. Med.Dośw., 2014; 68: 258‑270
  Google Scholar
• 63. Terendera M.: Badania nad znaczeniem prognostycznym wybranychmarkerów angiogenezy, proliferacji komórkowej i przerzutowaniau chorych operowanych z powodu raka żołądka – aktualnystan wiedzy. Wiad. Lek., 2006; 59: 855‑860
  Google Scholar
• 64. Terry M.B., Gaudet M.M., Gammon M.D.: The epidemiology ofgastric cancer. Semin. Radiat. Oncol. 2002; 12: 111‑127
  Google Scholar
• 65. Wang J.Y., Hsieh J.S., Chen C.C., Tzou W.S., Cheng T.L., Chen F.M.,Huang T.J., Huang Y.S., Yang T., Lin S.R.: Alterations of APC, c‑met,and p‑53 genes in tumor tissue and serum of patients with gastriccancer. J. Surg. Res., 2004; 120: 242‑248
  Google Scholar
• 66. Wang L., Yang M., Shan L., Qi L., Chai C., Zhou Q., Yao K., WuH., Sun W.: The role of SPARC protein expression in the progress ofgastric cancer. Pathol. Oncol. Res., 2012; 18: 697‑702
  Google Scholar
• 67. Wang X., Chen X., Fang J., Yang C.: Overexpression of bothVEGF‑A and VEGF‑C in gastric cancer correlates with prognosis,and silencing of both is effective to inhibit cancer growth. Int. J.Clin. Exp. Pathol., 2013; 6: 586‑597
  Google Scholar
• 68. Wideł M. S., Wideł M.: Mechanizmy przerzutowania i molekularnemarkery progresji nowotworów złośliwych. I. Rak jelita grubego.Postępy Hig. Med. Dośw., 2006; 60: 453‑470
  Google Scholar
• 69. Wu X., Chen X., Zhou Q., Li P., Yu B., Li J., Qu Y., Yan J., Yu Y., YanM., Zhu Z., Liu B., Su L.: Hepatocyte growth factor activates tumorstromal fibroblasts to promote tumorigenesis in gastric cancer. CancerLett., 2013; 335: 128‑135
  Google Scholar
• 70. Yaghoobi M., Bijarchi r., Narod S.A.: Family history and the riskof gastric cancer. Br. J. Cancer, 2010; 102: 237‑242
  Google Scholar
• 71. Yanchenko N., Sugihara H.: Integrin and E‑cadherin expressionalterations as a possible reason of undifferentiated‑type gastriccarcinoma diversity. W: Gastric Carcinoma – Molecular Aspects andCurrent Advances, red.: Lotfy M. InTech, 2011, 105‑122
  Google Scholar
• 72. York J.E., Stringer J., Ajani J.A., Wildrick D.M., Gokaslan Z.L.:Gastric cancer and metastasis to the brain. Ann. Surg. Oncol., 1999;6: 771‑776
  Google Scholar
• 73. Yoo N.J., Lee J.W., Kim Y.J., Soung Y.H., Kim S.Y., Nam S.W., ParkW.S., Lee J.Y., Lee S.H.: Loss of caspase‑2, – 6 and – 7 expression ingastric cancers. APMIS, 2004; 112: 330‑335
  Google Scholar
• 74. Zhang Z.Y., Ge H.Y.: Micrometastasis in gastric cancer. CancerLett., 2013; 336: 34‑45
  Google Scholar
• 75. Zhao B.C., Wang Z.J., Mao W.Z., Ma H.C., Han J.G., Zhao B., XuH.M.: CXCR4/SDF‑1 axis is involved in lymph node metastasis of gastriccarcinoma. World J. Gastroenterol., 2011; 17: 2389‑2396
  Google Scholar
• 76. Zhao C., Lu X., Bu X., Zhang N., Wang W.: Involvement of tumornecrosis factor‑α in the upregulation of CXCR4 expression in gastriccancer induced by Helicobacter pylori. BMC Cancer, 2010; 10: 419
  Google Scholar
• 77. Zhu S., Sun P., Zhang Y., Yan L., Luo B.: Expression of c‑myc andPCNA in Epstein‑Barr virus‑associated gastric carcinoma. Exp. Ther.Med., 2013; 5: 1030‑1034
  Google Scholar

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