Tumor Associated Macrophages as Major Promoters of Gastric Cancer_CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY

Authors：

ZHAO Junjie ,  QIN Jing , SHU Ping

Department of General Surgery， Zhongshan Hospital， Fudan University， Shanghai 200032， China;

Corresponding author：

QIN Jing, Email: qin.jing@zs-hospital.sh.cn

Keywords：

Macrophage; Tumor associated macrophages; Stomach malignant tumor; Review

Video：

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Abstract Full text Figures/Tables Video References Cited by

Objective 　To explore the association of macrophages with carcinogenesis and development of gastric cancer.
Method 　The related literatures at home and abroad were consulted and reviewed.
Results 　The microenvironment of gastric cancer could induce the polarization of macrophages，and then the activated macrophages，especially the tumor associated macrophages，could in turn motivate the growth，invasion，and metastasis of tumor cells by secreting a series of active substances.
Conclusions 　Macrophages，especially the tumor associated macrophages play an important
role in the carcinogenesis and development of gastric cancer. Investigating the macrophages and their interaction with gastric cancer may lead to a profound understanding of carcinogenesis of gastric cancer as well as opening up a new prospect
for treatment.

Citation： ZHAO Junjie,QIN Jing,SHU Ping. Tumor Associated Macrophages as Major Promoters of Gastric Cancer. CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY, 2013, 20(11): 1315-1319. doi: Copy

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2.	Gao L， Nieters A， Brenner H. Meta-analysis：tumour invasion-related genetic polymorphisms and gastric cancer susceptibility[J]. Aliment Pharmacol Ther， 2008， 28(5)：565-573.
3.	[J]. J Cell Sci， 2003， 116(Pt 4)：665-674.
4.	Sica A， Saccani A， Mantovani A. Tumor-associated macrophages：a molecular perspective[J]. Int Immunopharmacol， 2002， 2(8)：1045-1054.
5.	Mantovani A， Sica A， Sozzani S， et al. The chemokine system in diverse forms of macrophage activation and polarization[J]. Trends Immunol， 2004， 25(12)：677-686.
6.	Moon ML， McNeil LK， Freund GG. Macrophages make me sick：how macrophage activation states influence sickness behavior[J]. Psychoneuroendocrinology， 2011， 36(10)：1431-1440.
7.	Gordon S， Martinez FO. Alternative activation of macrophages：mechanism and functions[J]. Immunity， 2010， 32(5)：593-604.
8.	Sica A， Bronte V. Altered macrophage differentiation and immunedysfunction in tumor development[J]. J Clin Invest， 2007， 117(5)：1155-1166.
9.	Sica A， Schioppa T， Mantovani A， et al. Tumour-associated macrophages are a distinct M2 polarised population promoting tumour progression：potential targets of anti-cancer therapy[J]. Eur J Cancer， 2006， 42(6)：717-727.
10.	Solinas G， Schiarea S， Liguori M， et al. Tumor-conditioned macrophages secrete migration-stimulating factor：a new marker for M2-polarization， influencing tumor cell motility[J]. J Imm-unol， 2010， 185(1)：642-652. doi：10.4049/jimmunol. 1000413.
11.	Duluc D， Delneste Y， Tan F， et al. Tumor-associated leukemia inhibitory factor and IL-6 skew monocyte differentiation into tumor-associated macrophage-like cells[J]. Blood， 2007， 110(13)：4319-4330.
12.	Pollard JW. Tumour-educated macrophages promote tumour prog-ression and metastasis[J]. Nat Rev Cancer， 2004， 4(1)：71-78.
13.	Wang YC， He F， Feng F， et al. Notch signaling determines the M1 versus M2 polarization of macrophages in antitumor imm-une responses[J]. Cancer Res， 2010， 70(12)：4840-4849.
14.	Liu HC， Zheng MH， Du YL， et al. N9 microglial cells polarized by LPS and IL4 show differential responses to secondary environmental stimuli[J]. Cell Immunol， 2012， 278(1-2)：84-90.
15.	Mancino A， Lawrence T. Nuclear factor-kappa B and tumor-associated macrophages[J]. Clin Cancer Res， 2010，16(3)：784-789.
16.	Biswas SK， Gangi L， Paul S， et al. A distinct and unique transcriptional program expressed by tumor-associated macrophages (defective NF-kappa B and enhanced IRF-3/STAT1 activation)[J]. Blood， 2006， 107(5)：2112-2122.
17.	Biswas SK， Lewis CE. NF-κB as a central regulator of macrop-hage function in tumors[J]. J Leukoc Biol， 2010， 88(5)：877-884. doi：10.1189/jlb.0310153.
18.	Mantovani A， Sica A. Macrophages， innate immunity and cancer：balance， tolerance， and diversity[J]. Curr Opin Immunol， 2010，.
19.	Van Ginderachter JA， Movahedi K， Hassanzadeh GG， et al. Classical and alternative activation of mononuclear phagocytes：picking the best of both worlds for tumor promotion[J]. Immunobiology， 2006， 211(6-8)：487-501.
20.	Quiding-Jarbrink M， Raghavan S， Sundquist M. Enhanced M1 macrophage polarization in human helicobacter pylori-associated atrophic gastritis and in vaccinated mice[J]. PLoS One， 2010， 5(11)：e15018.
21.	Mosser DM， Edwards JP. Exploring the full spectrum of macro-phage activation[J]. Nat Rev Immunol， 2008， 8(12)：958-969. doi：10.1038/nri2448.
22.	Wu H， Xu JB， He YL， et al. Tumor-associated macrophages promote angiogenesis and lymphangiogenesis of gastric cancer[J]. J Surg Oncol， 2012， 106(4)：462-468. doi：10.1002/jso.
23.	(2)：231-237. doi：10.1016/j.coi.2010.01.009.
24.	Shen Z， Kauttu T， Seppanen H， et al. Vasohibin-1 and vasohibin-2 expression in gastric cancer cells and TAMs[J]. Med Oncol， 2012， 29(4)：2718-2726.
25.	Peng CW， Liu XL， Liu X， et al. Co-evolution of cancer microenvironment reveals distinctive patterns of gastric cancer invasion：laboratory evidence and clinical significance[J]. J Transl Med， 2010， 8：101. doi：10.1186/1479-5876-8-101.
26.	Kitadai Y. Cancer-stromal cell interaction and tumor angiogenesisin gastric cancer[J]. Cancer Microenviron， 2010， 3(1)：109-116. doi： 10.1007/s12307-009-0032-9.
27.	Ma YY， He XJ， Wang HJ， et al. Interaction of coagulation factors and tumor-associated macrophages mediates migration and invasion of gastric cancer[J]. Cancer Sci， 2011， 102(2)：336-342.
28.	Wu MH， Tsai YT， Hua KT， et al. Eicosapentaenoic acid and docosahexaenoic acid inhibit macrophage-induced gastric cancer cell migration by attenuating the expression of matrix metalloproteinase 10[J]. J Nutr Biochem， 2012， 23(11)：1434-1439.
29.	Shen Z， Ye Y， Kauttu T， et al. The novel focal adhesion gene kindlin-2 promotes the invasion of gastric cancer cells mediated by tumor-associated macrophages[J]. Oncol Rep， 2013， 29(2)：791-797.
30.	Takahashi A， Kono K， Ichihara F， et al. Macrophages in tumor-draining lymph node with different characteristics induce T-cell apoptosis in patients with advanced stage-gastric cancer[J]. Int J Cancer， 2003， 104(4)：393-399.
31.	Ohno S， Inagawa H， Dhar DK， et al. Role of tumor-associated macrophages (TAM) in advanced gastric carcinoma：the impact on FasL-mediated counterattack[J]. Anticancer Res， 2005， 25(1B)：463-470.
32.	Huang S. Regulation of metastases by signal transducer and activator of transcription 3 signaling pathway：clinical implications[J]. Clin Cancer Res， 2007， 13(5)：1362-1366.
33.	Clements WM， Wang J， Sarnaik A， et al. beta-catenin mutationis a frequent cause of Wnt pathway activation in gastric cancer[J].Cancer Res， 2002， 62(12)：3503-3506.
34.	Cheng XX， Wang ZC， Chen XY， et al. Correlation of Wnt-2 expression and beta-catenin intracellular accumulation in Chinese gastric cancers：relevance with tumour dissemination[J]. CancerLett， 2005， 223(2)：339-347.
35.	Kolligs F T， Bommer G， Goke B. Wnt/beta-catenin/tcf signaling：a critical pathway in gastrointestinal tumorigenesis[J]. Digestion， 2002， 66(3)：131-144.
36.	Oguma K， Oshima H， Aoki M， et al. Activated macrophages promote Wnt signalling through tumour necrosis factor-alpha in gastric tumour cells[J]. EMBO J， 2008， 27(12)：1671-1681.
37.	Oguma K， Oshima H， Oshima M. Inflammation， tumor necrosisfactor and Wnt promotion in gastric cancer development[J]. Future Oncol， 2010， 6(4)：515-526. doi：10.2217/fon.10.13.
38.	Zhao C， Ma H， Bu X， et al. SFRP5 inhibits gastric epithelial cell migration induced by macrophage-derived Wnt5a[J]. Car-cinogenesis， 2013， 34(1)：146-152.
39.	Kiriakidis S， Andreakos E， Monaco C， et al. VEGF expression in human macrophages is NF-kappa B-dependent：studies using adenoviruses expressing the endogenous NF-kappa B inhibitor Ikappa B alpha and a kinase-defective form of the I kappa B kinase.
40.	Watari K， Nakao S， Fotovati A， et al. Role of macrophages in inflammatory lymphangiogenesis：Enhanced production of vascular endothelial growth factor C and D through NF-kappa B activation[J]. Biochem Biophys Res Commun， 2008， 377(3)：826-831.
41.	Yang J， Weinberg RA. Epithelial-mesenchymal transition：at the crossroads of development and tumor metastasis[J]. Dev Cell， 2008， 14(6)：818-829.
42.	Mani SA， Guo W， Liao MJ， et al. The epithelial-mesenchymal transition generates cells with properties of stem cells[J]. Cell， 2008， 133(4)：704-715.
43.	Wu Y， Deng J， Rychahou PG， et al. Stabilization of snail by NF-kappa B is required for inflammation-induced cell migration and invasion[J]. Cancer Cell， 2009， 15(5)：416-428.
44.	Bonde AK， Tischler V， Kumar S， et al. Intratumoral macrophagescontribute to epithelial-mesenchymal transition in solid tumors[J]. BMC Cancer， 2012， 12：35. doi：10.1186/1471-2407-12-35.
45.	Zhang QW， Liu L， Gong CY， et al. Prognostic significance of tumor-associated macrophages in solid tumor：a meta-analysis of the literature[J]. PLoS One， 2012， 7(12)：e50946.
46.	Kawahara A， Hattori S， Akiba J， et al. Infiltration of thymidine phosphorylase-positive macrophages is closely associated with tumor angiogenesis and survival in intestinal type gastric cancer[J]. Oncol Rep， 2010， 24(2)：405-415.
47.	束平，秦净，秦新裕，等. M2型巨噬细胞和调节性T细胞在胃癌组织中的表达及其预后预测价值[J]. 中华胃肠外科杂志， 2011， 14(5)：368-371.
48.	.

1. Inoue M， Tsugane S. Epidemiology of gastric cancer in Japan[J]. Postgrad Med J， 2005， 81(957)：419-424.
2. Gao L， Nieters A， Brenner H. Meta-analysis：tumour invasion-related genetic polymorphisms and gastric cancer susceptibility[J]. Aliment Pharmacol Ther， 2008， 28(5)：565-573.
3. [J]. J Cell Sci， 2003， 116(Pt 4)：665-674.
4. Sica A， Saccani A， Mantovani A. Tumor-associated macrophages：a molecular perspective[J]. Int Immunopharmacol， 2002， 2(8)：1045-1054.
5. Mantovani A， Sica A， Sozzani S， et al. The chemokine system in diverse forms of macrophage activation and polarization[J]. Trends Immunol， 2004， 25(12)：677-686.
6. Moon ML， McNeil LK， Freund GG. Macrophages make me sick：how macrophage activation states influence sickness behavior[J]. Psychoneuroendocrinology， 2011， 36(10)：1431-1440.
7. Gordon S， Martinez FO. Alternative activation of macrophages：mechanism and functions[J]. Immunity， 2010， 32(5)：593-604.
8. Sica A， Bronte V. Altered macrophage differentiation and immunedysfunction in tumor development[J]. J Clin Invest， 2007， 117(5)：1155-1166.
9. Sica A， Schioppa T， Mantovani A， et al. Tumour-associated macrophages are a distinct M2 polarised population promoting tumour progression：potential targets of anti-cancer therapy[J]. Eur J Cancer， 2006， 42(6)：717-727.
10. Solinas G， Schiarea S， Liguori M， et al. Tumor-conditioned macrophages secrete migration-stimulating factor：a new marker for M2-polarization， influencing tumor cell motility[J]. J Imm-unol， 2010， 185(1)：642-652. doi：10.4049/jimmunol. 1000413.
11. Duluc D， Delneste Y， Tan F， et al. Tumor-associated leukemia inhibitory factor and IL-6 skew monocyte differentiation into tumor-associated macrophage-like cells[J]. Blood， 2007， 110(13)：4319-4330.
12. Pollard JW. Tumour-educated macrophages promote tumour prog-ression and metastasis[J]. Nat Rev Cancer， 2004， 4(1)：71-78.
13. Wang YC， He F， Feng F， et al. Notch signaling determines the M1 versus M2 polarization of macrophages in antitumor imm-une responses[J]. Cancer Res， 2010， 70(12)：4840-4849.
14. Liu HC， Zheng MH， Du YL， et al. N9 microglial cells polarized by LPS and IL4 show differential responses to secondary environmental stimuli[J]. Cell Immunol， 2012， 278(1-2)：84-90.
15. Mancino A， Lawrence T. Nuclear factor-kappa B and tumor-associated macrophages[J]. Clin Cancer Res， 2010，16(3)：784-789.
16. Biswas SK， Gangi L， Paul S， et al. A distinct and unique transcriptional program expressed by tumor-associated macrophages (defective NF-kappa B and enhanced IRF-3/STAT1 activation)[J]. Blood， 2006， 107(5)：2112-2122.
17. Biswas SK， Lewis CE. NF-κB as a central regulator of macrop-hage function in tumors[J]. J Leukoc Biol， 2010， 88(5)：877-884. doi：10.1189/jlb.0310153.
18. Mantovani A， Sica A. Macrophages， innate immunity and cancer：balance， tolerance， and diversity[J]. Curr Opin Immunol， 2010，.
19. Van Ginderachter JA， Movahedi K， Hassanzadeh GG， et al. Classical and alternative activation of mononuclear phagocytes：picking the best of both worlds for tumor promotion[J]. Immunobiology， 2006， 211(6-8)：487-501.
20. Quiding-Jarbrink M， Raghavan S， Sundquist M. Enhanced M1 macrophage polarization in human helicobacter pylori-associated atrophic gastritis and in vaccinated mice[J]. PLoS One， 2010， 5(11)：e15018.
21. Mosser DM， Edwards JP. Exploring the full spectrum of macro-phage activation[J]. Nat Rev Immunol， 2008， 8(12)：958-969. doi：10.1038/nri2448.
22. Wu H， Xu JB， He YL， et al. Tumor-associated macrophages promote angiogenesis and lymphangiogenesis of gastric cancer[J]. J Surg Oncol， 2012， 106(4)：462-468. doi：10.1002/jso.
23. (2)：231-237. doi：10.1016/j.coi.2010.01.009.
24. Shen Z， Kauttu T， Seppanen H， et al. Vasohibin-1 and vasohibin-2 expression in gastric cancer cells and TAMs[J]. Med Oncol， 2012， 29(4)：2718-2726.
25. Peng CW， Liu XL， Liu X， et al. Co-evolution of cancer microenvironment reveals distinctive patterns of gastric cancer invasion：laboratory evidence and clinical significance[J]. J Transl Med， 2010， 8：101. doi：10.1186/1479-5876-8-101.
26. Kitadai Y. Cancer-stromal cell interaction and tumor angiogenesisin gastric cancer[J]. Cancer Microenviron， 2010， 3(1)：109-116. doi： 10.1007/s12307-009-0032-9.
27. Ma YY， He XJ， Wang HJ， et al. Interaction of coagulation factors and tumor-associated macrophages mediates migration and invasion of gastric cancer[J]. Cancer Sci， 2011， 102(2)：336-342.
28. Wu MH， Tsai YT， Hua KT， et al. Eicosapentaenoic acid and docosahexaenoic acid inhibit macrophage-induced gastric cancer cell migration by attenuating the expression of matrix metalloproteinase 10[J]. J Nutr Biochem， 2012， 23(11)：1434-1439.
29. Shen Z， Ye Y， Kauttu T， et al. The novel focal adhesion gene kindlin-2 promotes the invasion of gastric cancer cells mediated by tumor-associated macrophages[J]. Oncol Rep， 2013， 29(2)：791-797.
30. Takahashi A， Kono K， Ichihara F， et al. Macrophages in tumor-draining lymph node with different characteristics induce T-cell apoptosis in patients with advanced stage-gastric cancer[J]. Int J Cancer， 2003， 104(4)：393-399.
31. Ohno S， Inagawa H， Dhar DK， et al. Role of tumor-associated macrophages (TAM) in advanced gastric carcinoma：the impact on FasL-mediated counterattack[J]. Anticancer Res， 2005， 25(1B)：463-470.
32. Huang S. Regulation of metastases by signal transducer and activator of transcription 3 signaling pathway：clinical implications[J]. Clin Cancer Res， 2007， 13(5)：1362-1366.
33. Clements WM， Wang J， Sarnaik A， et al. beta-catenin mutationis a frequent cause of Wnt pathway activation in gastric cancer[J].Cancer Res， 2002， 62(12)：3503-3506.
34. Cheng XX， Wang ZC， Chen XY， et al. Correlation of Wnt-2 expression and beta-catenin intracellular accumulation in Chinese gastric cancers：relevance with tumour dissemination[J]. CancerLett， 2005， 223(2)：339-347.
35. Kolligs F T， Bommer G， Goke B. Wnt/beta-catenin/tcf signaling：a critical pathway in gastrointestinal tumorigenesis[J]. Digestion， 2002， 66(3)：131-144.
36. Oguma K， Oshima H， Aoki M， et al. Activated macrophages promote Wnt signalling through tumour necrosis factor-alpha in gastric tumour cells[J]. EMBO J， 2008， 27(12)：1671-1681.
37. Oguma K， Oshima H， Oshima M. Inflammation， tumor necrosisfactor and Wnt promotion in gastric cancer development[J]. Future Oncol， 2010， 6(4)：515-526. doi：10.2217/fon.10.13.
38. Zhao C， Ma H， Bu X， et al. SFRP5 inhibits gastric epithelial cell migration induced by macrophage-derived Wnt5a[J]. Car-cinogenesis， 2013， 34(1)：146-152.
39. Kiriakidis S， Andreakos E， Monaco C， et al. VEGF expression in human macrophages is NF-kappa B-dependent：studies using adenoviruses expressing the endogenous NF-kappa B inhibitor Ikappa B alpha and a kinase-defective form of the I kappa B kinase.
40. Watari K， Nakao S， Fotovati A， et al. Role of macrophages in inflammatory lymphangiogenesis：Enhanced production of vascular endothelial growth factor C and D through NF-kappa B activation[J]. Biochem Biophys Res Commun， 2008， 377(3)：826-831.
41. Yang J， Weinberg RA. Epithelial-mesenchymal transition：at the crossroads of development and tumor metastasis[J]. Dev Cell， 2008， 14(6)：818-829.
42. Mani SA， Guo W， Liao MJ， et al. The epithelial-mesenchymal transition generates cells with properties of stem cells[J]. Cell， 2008， 133(4)：704-715.
43. Wu Y， Deng J， Rychahou PG， et al. Stabilization of snail by NF-kappa B is required for inflammation-induced cell migration and invasion[J]. Cancer Cell， 2009， 15(5)：416-428.
44. Bonde AK， Tischler V， Kumar S， et al. Intratumoral macrophagescontribute to epithelial-mesenchymal transition in solid tumors[J]. BMC Cancer， 2012， 12：35. doi：10.1186/1471-2407-12-35.
45. Zhang QW， Liu L， Gong CY， et al. Prognostic significance of tumor-associated macrophages in solid tumor：a meta-analysis of the literature[J]. PLoS One， 2012， 7(12)：e50946.
46. Kawahara A， Hattori S， Akiba J， et al. Infiltration of thymidine phosphorylase-positive macrophages is closely associated with tumor angiogenesis and survival in intestinal type gastric cancer[J]. Oncol Rep， 2010， 24(2)：405-415.
47. 束平，秦净，秦新裕，等. M2型巨噬细胞和调节性T细胞在胃癌组织中的表达及其预后预测价值[J]. 中华胃肠外科杂志， 2011， 14(5)：368-371.
48. .

CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY

Tumor Associated Macrophages as Major Promoters of Gastric Cancer

Abstract Full text Figures/Tables Video References Cited by

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