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Cancer Microenvironment
Erschienen in: Cancer Microenvironment 3/2012

01.12.2012 | Review Article

Inflammatory Immune Responses in Tumor Microenvironment and Metastasis of Hepatocellular Carcinoma

verfasst von: Lun-Xiu Qin

Erschienen in: Cancer Microenvironment | Ausgabe 3/2012

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Abstract

Metastasis is a multistage process that requires cancer cells to escape from the primary tumor, survive in the circulation, seed at distant sites and grow. Each of these processes involves rate-limiting steps that are influenced by non-malignant cells of the tumor microenvironment. There are growing evidences that tumors are sustained and promoted by inflammatory signals from the surrounding microenvironment. This review describes experimental data demonstrating the role of the inflammatory immune responses of microenvironment in metastases of hepatocellular carcinoma (HCC), points out the prospective areas for future research and possible new therapeutic approaches to control the metastasis of HCC.
Literatur
1.
He J, Gu D, Wu X, Reynolds K, Duan X, Yao C, Wang J, Chen CS, Chen J, Wildman RP, Klag MJ, Whelton PK (2005) Major causes of death among men and women in China. N Engl J Med 353:1124–1134PubMedCrossRef
2.
Parkin DM, Bray F, Ferlay J, Pisani P (2002) Global cancer statistics,2005. CA Cancer J Clin 55:74–108CrossRef
3.
Portolani N, Coniglio A, Ghidoni S, Giovanelli M, Benetti A, Tiberio GA, Giulini SM (2006) Early and late recurrence after liver resection for hepatocellular carcinoma: prognostic and therapeutic implications. Ann Surg 243:229–235PubMedCrossRef
4.
Yeung YP, Lo CM, Liu CL, Wong BC, Fan ST, Wong J (2005) Natural history of untreated nonsurgical hepatocellular carcinoma. Am J Gastroenterol 100:1995–2004PubMedCrossRef
5.
Chaffer CL, Weinberg RA (2011) A perspective on cancer cell metastasis. Science 331:1559–1564PubMedCrossRef
6.
7.
8.
Schrader J, Iredale JP (2011) The inflammatory microenvironment of HCC – the plot becomes complex. J Hepatol 54:853–855PubMedCrossRef
9.
Yang JD, Nakamura I, Roberts LR (2011) The tumor microenvironment in hepatocellular carcinoma: current status and therapeutic targets. Semin Cancer Biol 21:35–43PubMedCrossRef
10.
Mantovani A, Allavena P, Sica A, Balkwill F (2008) Cancer-related inflammation. Nature 54:436–444CrossRef
11.
12.
El-Serag HB, Rudolph KL (2007) Hepatocellular carcinoma: epidemiology and molecular carcinogenesis. Gastroenterology 132:2557–2576PubMedCrossRef
13.
Budhu A, Forgues M, Ye QH, Jia HL, He P, Zanetti KA, Kammula US, Chen Y, Qin LX, Tang ZY, Wang XW (2006) Prediction of venous metastases, recurrence, and prognosis in hepatocellular carcinoma based on a unique immune response signature of the liver microenvironment. Cancer Cell 10:99–111PubMedCrossRef
14.
Wang Y, Kato N, Hoshida Y, Yoshida H, Taniguchi H, Goto T, Moriyama M, Otsuka M, Shiina S, Shiratori Y, Ito Y, Omata M (2003) Interleukin-1β gene polymorphisms associated with hepatocellular carcinoma in hepatitis C virus infection. Hepatology 37:65–71PubMedCrossRef
15.
Migita K, Miyazoe S, Maeda Y, Daikoku M, Abiru S, Ueki T, Yano K, Nagaoka S, Matsumoto T, Nakao K, Hamasaki K, Yatsuhashi H, Ishibashi H, Eguchi K (2005) Cytokine gene polymorphisms in Japanese patients with hepatitis B virus infection–association between TGF-β1 polymorphisms and hepatocellular carcinoma. J Hepatol 42:505–510PubMedCrossRef
16.
Grivennikov SI, Greten FR, Karin M (2010) Immunity, inflammation, and cancer. Cell 140:883–899PubMedCrossRef
17.
Grivennikov SI, Karin M (2010) Dangerous liaisons: STAT3 and NF-kappaB collaboration and crosstalk in cancer. Cytokine Growth Factor Rev 21:11–19PubMedCrossRef
18.
Anson M, Crain-Denoyelle AM, Baud V, Chereau F, Gougelet A, Terris B, Yamagoe S, Colnot S, Viguier M, Perret C, Couty JP (2012) Oncogenic β-catenin triggers an inflammatory response that determines the aggressiveness of hepatocellular carcinoma in mice. J Clin Invest 122:586–599PubMedCrossRef
19.
Han YP, Zhou L, Wang J, Xiong S, Garner WL, French SW, Tsukamoto H (2004) Essential role of matrix metalloproteinases in interleukin-1-induced myofibroblastic activation of hepatic stellate cell in collagen. J Biol Chem 279:4820–4828PubMedCrossRef
20.
21.
Wang Y, Wang W, Wang L, Wang X, Xia J (2011) Regulatory mechanisms of interleukin 8 production induced by tumor necrosis factor-alpha in human hepatocellular carcinoma cells. J Cell Mol Med 16:496–506CrossRef
22.
Park EJ, Lee JH, Yu GY, He G, Ali SR, Holzer RG, Osterreicher CH, Takahashi H, Karin M (2010) Dietary and genetic obesity promote liver inflammation and tumorigenesis by enhancing IL-6 and TNF expression. Cell 140:197–208PubMedCrossRef
23.
Xiang WQ, Feng WF, Ke W, Sun Z, Chen Z, Liu W (2011) Hepatitis B virus X protein stimulates IL-6 expression in hepatocytes via a MyD88-dependent pathway. J Hepatol 54:26–33PubMedCrossRef
24.
Trinchieri G (2003) Interleukin-12 and the regulation of innate resistance and adaptive immunity. Nat Rev Immunol 3:133–146PubMedCrossRef
25.
Jiang R, Tan Z, Deng L, Chen Y, Xia Y, Gao Y, Wang X, Sun B (2011) Interleukin-22 promotes human hepatocellular carcinoma by activation of STAT3. Hepatology 54:900–909PubMedCrossRef
26.
Hoshida Y, Nijman SM, Kobayashi M, Chan JA, Brunet JP, Chiang DY, Villanueva A, Newell P, Ikeda K, Hashimoto M, Watanabe G, Gabriel S, Friedman SL, Kumada H, Llovet JM, Golub TR (2009) Integrative transcriptome analysis reveals common molecular subclasses of human hepatocellular carcinoma. Cancer Res 69:7385–7392PubMedCrossRef
27.
Coulouarn C, Factor VM, Thorgeirsson SS (2008) Transforming growth factor-beta gene expression signature in mouse hepatocytes predicts clinical outcome in human cancer. Hepatology 47:2059–2067PubMedCrossRef
28.
Lee JS, Heo J, Libbrecht L, Chu IS, Kaposi-Novak P, Calvisi DF, Mikaelyan A, Roberts LR, Demetris AJ, Sun Z, Nevens F, Roskams T, Thorgeirsson SS (2006) A novel prognostic subtype of human hepatocellular carcinoma derived from hepatic progenitor cells. Nat Med 12:410–416PubMedCrossRef
29.
Okamoto M, Utsunomiya T, Wakiyama S, Hashimoto M, Fukuzawa K, Ezaki T, Hanai T, Inoue H, Mori M (2006) Specific gene-expression profiles of noncancerous liver tissue predict the risk for multicentric occurrence of hepatocellular carcinoma in hepatitis C virus-positive patients. Ann Surg Oncol 13:947–954PubMedCrossRef
30.
Woo HG, Park ES, Cheon JH, Kim JH, Lee JS, Park BJ, Kim W, Park SC, Chung YJ, Kim BG, Yoon JH, Lee HS, Kim CY, Yi NJ, Suh KS, Lee KU, Chu IS, Roskams T, Thorgeirsson SS, Kim YJ (2008) Gene expression-based recurrence prediction of hepatitis B virus-related human hepatocellular carcinoma. Clin Cancer Res 14:2056–2064PubMedCrossRef
31.
Hoshida Y, Villanueva A, Kobayashi M, Peix J, Chiang DY, Camargo A, Gupta S, Moore J, Wrobel MJ, Lerner J, Reich M, Chan JA, Glickman JN, Ikeda K, Hashimoto M, Watanabe G, Daidone MG, Roayaie S, Schwartz M, Thung S, Salvesen HB, Gabriel S, Mazzaferro V, Bruix J, Friedman SL, Kumada H, Llovet JM, Golub TR (2008) Gene expression in fixed tissues and outcome in hepatocellular carcinoma. N Engl J Med 359:1995–2004PubMedCrossRef
32.
Chew V, Chen J, Lee D, Loh E, Lee J, Lim KH, Weber A, Slankamenac K, Poon RT, Yang H, Ooi LL, Toh HC, Heikenwalder M, Ng IO, Nardin A, Abastado JP (2012) Chemokine-driven lymphocyte infiltration: an early intratumoural event determining long-term survival in resectable hepatocellular carcinoma. Gut 61:427–438PubMedCrossRef
33.
Zhou HJ, Huang H, Shi J, Zhao Y, Dong QZ, Jia HL, Liu YK, Ye QH, Sun HC, Zhu XD, Fu LY, Guo K, Gao DM, Sun J, Yan ZW, Ren N, Tang ZY, Qin LX (2010) The prognostic value of IL-2 and IL-15 in peritumoral hepatic tissues for hepatocellular carcinoma patients after curative resection. Gut 59:1699–1708PubMedCrossRef
34.
Pang YL, Zhang HG, Peng JR, Pang XW, Yu S, Xing Q, Yu X, Gong L, Yin YH, Zhang Y, Chen WF (2009) The immunosuppressive tumor microenvironment in hepatocellular carcinoma. Cancer Immunol Immunother 58:877–886PubMedCrossRef
35.
Yakirevich E, Resnick MB (2007) Regulatory T lymphocytes: pivotal components of the host antitumor response. J Clin Oncol 25:2506–2508PubMedCrossRef
36.
Fu J, Xu D, Liu Z, Shi M, Zhao P, Fu B, Zhang Z, Yang H, Zhang H, Zhou C, Yao J, Jin L, Wang H, Yang Y, Fu YX, Wang FS (2007) Increased regulatory T cells correlate with CD8 T cell impairment and poor survival in hepatocellular carcinoma patients. Gastroenterology 132:2328–2339PubMedCrossRef
37.
Gao Q, Qiu SJ, Fan J, Zhou J, Wang XY, Xiao YS, Xu Y, Li YW, Tang ZY (2007) Intratumoral balance of regulatory and cytotoxic T cells is associated with prognosis of hepatocellular carcinoma after resection. J Clin Oncol 25:2586–2593PubMedCrossRef
38.
Cai MY, Xu YF, Qiu SJ, Ju MJ, Gao Q, Li YW, Zhang BH, Zhou J, Fan J (2009) Human leukocyte antigen-G protein expression is an unfavorable prognostic predictor of hepatocellular carcinoma following curative resection. Clin Cancer Res 15:4686–4693PubMedCrossRef
39.
Chen KJ, Lin SZ, Zhou L, Xie HY, Zhou WH, Taki-Eldin A, Zheng SS (2011) Selective recruitment of regulatory T cell through CCR6-CCL20 in hepatocellular carcinoma fosters tumor progression and predicts poor prognosis. PLoS One 6:e24671PubMedCrossRef
40.
Gao Q, Zhou J, Wang XY, Qiu SJ, Song K, Huang XW, Sun J, Shi YH, Li BZ, Xiao YS, Fan J (2012) Infiltrating memory/senescent T cell ratio predicts extrahepatic metastasis of hepatocellular carcinoma. Ann Surg Oncol 19:455–466PubMedCrossRef
41.
Cai L, Zhang Z, Zhou L, Wang H, Fu J, Zhang S, Shi M, Zhang H, Yang Y, Wu H, Tien P, Wang FS (2008) Functional impairment in circulating and intrahepatic NK cells and relative mechanism in hepatocellular carcinoma patients. Clin Immunol 129:428–437PubMedCrossRef
42.
Ghiringhelli F, Ménard C, Martin F, Zitvogel L (2006) The role of regulatory T cells in the control of natural killer cells: relevance during tumor progression. Immunol Rev 214:229–238PubMedCrossRef
43.
Bergmann C, Wild CA, Narwan M, Lotfi R, Lang S, Brandau S (2011) Human tumor-induced and naturally occurring Treg cells differentially affect NK cells activated by either IL-2 or target cells. Eur J Immunol 41:3564–3573PubMedCrossRef
44.
Shirabe K, Mano Y, Muto J, Matono R, Motomura T, Toshima T, Takeishi K, Uchiyama H, Yoshizumi T, Taketomi A, Morita M, Tsujitani S, Sakaguchi Y, Maehara Y (2012) Role of tumor-associated macrophages in the progression of hepatocellular carcinoma. Surg Today 42:1–7PubMedCrossRef
45.
Verreck FA, de Boer T, Langenberg DM, Hoeve MA, Kramer M, Vaisberg E, Kastelein R, Kolk A, de Waal-Malefyt R, Ottenhoff TH (2004) Human IL-23-producing type 1 macrophages promote but IL-10-producing type 2 macrophages subvert immunity to (myco) bacteria. Proc Natl Acad Sci USA 101:4560–4565PubMedCrossRef
46.
Zhu XD, Zhang JB, Zhuang PY, Zhu HG, Zhang W, Xiong YQ, Wu WZ, Wang L, Tang ZY, Sun HC (2008) High expression of macrophage colony-stimulating factor in peritumoral liver tissue is associated with poor survival after curative resection of hepatocellular carcinoma. J Clin Oncol 26:2707–2716PubMedCrossRef
47.
Wu K, Kryczek I, Chen L, Zou W, Welling TH (2009) Kupffer cell suppression of CD8+ T cells in human hepatocellular carcinoma is mediated by B7-H1/programmed death-1 interactions. Cancer Res 69:8067–8075PubMedCrossRef
48.
Ramaiah SK, Rittling S (2008) Pathophysiological role of osteopontin in hepatic inflammation, toxicity, and cancer. Toxicol Sci 103:4–13PubMedCrossRef
49.
Ye QH, Qin LX, Forgues M, He P, Kim JW, Peng AC, Simon R, Li Y, Robles AI, Chen YD, Ma ZC, Wu ZQ, Ye SL, Liu YK, Tang ZY, Wang XW (2003) Predicting hepatitis B virus-positive metastatic hepatocellular carcinomas using gene expression profiling and supervised machine learning. Nat Med 9:416–423PubMedCrossRef
50.
Sun BS, Ye QH, Ren N, Jia HL, Liu DY, Sun HJ, Zhou HJ, Chen J, Qin LX (2008) Lentiviral-mediated silencing of Osteopontin through RNA interference suppresses invasiveness and tumorigenicity of liver cancer cells. Hepatology 48:1834–1842PubMedCrossRef
51.
Xue YH, Zhang XF, Dong QZ, Sun J, Fu LY, Zhou HJ, Ren N, Jia HL, Ye QH, Qin LX (2010) Thrombin is a therapeutic target for metastatic osteopontin-positive hepatocellular carcinoma. Hepatology 52:2012–2022PubMedCrossRef
52.
De Wever O, Demetter P, Mareel M, Bracke M (2008) Stromal myofibroblasts are drivers of invasive cancer growth. Int J Cancer 123:2229–2238PubMedCrossRef
53.
Sun HC, Tang ZY, Wang L, Qin LX, Ma ZC, Ye QH, Zhang BH, Qian YB, Wu ZQ, Fan J, Zhou XD, Zhou J, Qiu SJ, Shen YF (2006) Postoperative interferon alpha treatment postponed recurrence and improved overall survival in patients after curative resection of HBV-related hepatocellular carcinoma: a randomized clinical trial. J Cancer Res Clin Oncol 132:458–465PubMedCrossRef
54.
Wang L, Tang ZY, Qin LX, Wu XF, Sun HC, Xue Q, Ye SL (2000) High-dose and long-term therapy with interferon-alfa inhibits tumor growth and recurrence in nude mice bearing human hepatocellular carcinoma xenografts with high metastatic potential. Hepatology 32:43–48PubMedCrossRef
55.
Ji J, Shi J, Budhu A, Yu Z, Forgues M, Roessler S, Ambs S, Chen Y, Meltzer PS, Croce CM, Qin LX, Man K, Lo CM, Lee J, Ng IO, Fan J, Tang ZY, Sun HC, Wang XW (2009) MicroRNA expression, survival, and response to interferon in liver cancer. N Engl J Med 361:1437–1447PubMedCrossRef
56.
Wang YC, Xu GL, Jia WD, Han SJ, Ren WH, Wang W, Liu WB, Zhang CH, Chen H (2012) Estrogen suppresses metastasis in rat hepatocellular carcinoma through decreasing Interleukin-6 and hepatocyte growth factor expression. Inflammation 35:143–149PubMedCrossRef
57.
Chew V, Tow C, Teo M, Wong HL, Chan J, Gehring A, Loh M, Bolze A, Quek R, Lee VK, Lee KH, Abastado JP, Toh HC, Nardin A (2010) Inflammatory tumour microenvironment is associated with superior survival in hepatocellular carcinoma patients. J Hepatol 52:370–379PubMedCrossRef
58.
Zhang W, Zhu XD, Sun HC, Xiong YQ, Zhuang PY, Xu HX, Kong LQ, Wang L, Wu WZ, Tang ZY (2010) Depletion of tumor-associated macrophages enhances the effect of sorafenib in metastatic liver cancer models by antimetastatic and antiangiogenic effects. Clin Cancer Res 16:3420–3430PubMedCrossRef
Metadaten
Titel
Inflammatory Immune Responses in Tumor Microenvironment and Metastasis of Hepatocellular Carcinoma
verfasst von
Lun-Xiu Qin
Publikationsdatum
01.12.2012
Verlag
Springer Netherlands
Erschienen in
Cancer Microenvironment / Ausgabe 3/2012
Print ISSN: 1875-2292
Elektronische ISSN: 1875-2284
DOI
https://doi.org/10.1007/s12307-012-0111-1

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