Asian Pacific Journal of Cancer Prevention

  • 제16권7호
  • /
  • Pages.3043-3050
  • /
  • 2015
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  • 1513-7368(pISSN)
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  • 2476-762X(eISSN)
아시아태평양암예방학회 (Asian Pacific Journal of Cancer Prevention)
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Quantitative Changes in Tumor-Associated M2 Macrophages Characterize Cholangiocarcinoma and their Association with Metastasis

  • Thanee, Malinee (Department of Biochemistry, Faculty of Medicine, Khon Kaen University) ;
  • Loilome, Watcharin (Department of Biochemistry, Faculty of Medicine, Khon Kaen University) ;
  • Techasen, Anchalee (Center for Research and Development of Medical Diagnostic Laboratories, Faculty of Associated Medical Sciences, Khon Kaen University) ;
  • Namwat, Nisana (Department of Biochemistry, Faculty of Medicine, Khon Kaen University) ;
  • Boonmars, Thidarut (Department of Parasitology, Faculty of Medicine, Khon Kaen University) ;
  • Pairojkul, Chawalit (Department of Pathology, Faculty of Medicine, Khon Kaen University) ;
  • Yongvanit, Puangrat (Department of Biochemistry, Faculty of Medicine, Khon Kaen University)
  • 발행 : 2015.04.14
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The tumor microenvironment (TME) includes numerous non-neoplastic cells such as leukocytes and fibroblasts that surround the neoplasm and influence its growth. Tumor-associated macrophages (TAMs) and cancerassociated fibroblasts (CAFs) are documented as key players in facilitating cancer appearance and progression. Alteration of the macrophage (CD68, CD163) and fibroblast (${\alpha}-SMA$, FSP-1) cells in Opisthorchis viverrini (Ov) -induced cholangiocarcinoma (CCA) was here assessed using liver tissues from an established hamster model and from 43 human cases using immunohistochemistry. We further investigated whether M2-activated TAMs influence CCA cell migration ability by wound healing assay and Western blot analysis. Macrophages and fibroblasts change their phenotypes to M2-TAMs (CD68+, CD163+) and CAFs (${\alpha}-SMA+$, FSP-1+), respectively in the early stages of carcinogenesis. Interestingly, a high density of the M2-TAMs CCA in patients is significantly associated with the presence of extrahepatic metastases (p=0.021). Similarly, CD163+ CCA cells are correlated with metastases (p=0.002), and they may be representative of an epithelial-to-mesenchymal transition (EMT) with increased metastatic activity. We further showed that M2-TAM conditioned medium can induce CCA cell migration as well as increase N-cadherin expression (mesenchymal marker). The present work revealed that significant TME changes occur at an early stage of Ov-induced carcinogenesis and that M2-TAMs are key factors contributing to CCA metastasis, possibly via EMT processes.

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참고문헌

  1. Adjei IM, Blanka S (2015). Modulation of the tumor microenvironment for cancer treatment: a biomaterials approach. J Funct Biomater, 6, 81-103. https://doi.org/10.3390/jfb6010081
  2. Albini A, Sporn MB (2007). The tumour microenvironment as a target for chemoprevention. Nat Rev Cancer, 7, 139-47.
  3. Bhamarapravati N, Thammavit W, Vajrasthira S (1978). Liver changes in hamsters infected with a liver fluke of man, Opisthorchis viverrini. Am J Trop Med Hyg, 27, 787-94.
  4. Campbell DJ, Dumur CI, Lamour NF, et al (2012). Novel organotypic culture model of cholangiocarcinoma progression. Hepatol Res, 42, 1119-30. https://doi.org/10.1111/j.1872-034X.2012.01026.x
  5. Chen SJ, Zhang QB, Zeng LJ, et al (2015). Distribution and clinical significance of tumour-associated macrophages in pancreatic ductal adenocarcinoma: a retrospective analysis in China. Curr Oncol, 22, 11-9.
  6. Chuaysri C, Thuwajit P, Paupairoj A, et al (2009). Alphasmooth muscle actin-positive fibroblasts promote biliary cell proliferation and correlate with poor survival in cholangiocarcinoma. Oncol Rep, 21, 957-69.
  7. Condeelis J, Pollard JW (2006). Macrophages: obligate partners for tumor cell migration, invasion, and metastasis. Cell, 124, 263-6. https://doi.org/10.1016/j.cell.2006.01.007
  8. De Wever O, Demetter P, Mareel M, et al (2008). Stromal myofibroblasts are drivers of invasive cancer growth. Int J Cancer, 123, 2229-38. https://doi.org/10.1002/ijc.23925
  9. Diaz R, Kim JW, Hui JJ, et al (2008). Evidence for the epithelial to mesenchymal transition in biliary atresia fibrosis. Hum Pathol, 39, 102-15. https://doi.org/10.1016/j.humpath.2007.05.021
  10. Ebralidze A, Tulchinsky E, Grigorian M, et al (1989). Isolation and characterization of a gene specifically expressed in different metastatic cells and whose deduced gene product has a high degree of homology to a Ca2+-binding protein family. Genes Dev, 3, 1086-93. https://doi.org/10.1101/gad.3.7.1086
  11. Erez N, Truitt M, Olson P, et al (2010). Cancer-Associated Fibroblasts Are Activated in Incipient Neoplasia to Orchestrate Tumor-Promoting Inflammation in an NF-kappaB-Dependent Manner. Cancer Cell, 17, 135-47. https://doi.org/10.1016/j.ccr.2009.12.041
  12. Forssell J, Oberg A, Henriksson ML, et al (2007). High macrophage infiltration along the tumor front correlates with improved survival in colon cancer. Clin Cancer Res, 13, 1472-9. https://doi.org/10.1158/1078-0432.CCR-06-2073
  13. Hasita H, Komohara Y, Okabe H, et al (2010). Significance of alternatively activated macrophages in patients with intrahepatic cholangiocarcinoma. Cancer Sci, 101, 1913-9. https://doi.org/10.1111/j.1349-7006.2010.01614.x
  14. Hazan RB, Phillips GR, Qiao RF, et al (2000). Exogenous expression of N-cadherin in breast cancer cells induces cell migration, invasion, and metastasis. J Cell Biol, 148, 779-90. https://doi.org/10.1083/jcb.148.4.779
  15. Hsu SM, Raine L (1981). Protein A, avidin, and biotin in immunohistochemistry. J Histochem Cytochem, 29, 1349-53. https://doi.org/10.1177/29.11.6172466
  16. Huang M, Li Y, Zhang H, et al (2010). Breast cancer stromal fibroblasts promote the generation of CD44+CD24- cells through SDF-1/CXCR4 interaction. J Exp Clin Cancer Res, 29, 80. https://doi.org/10.1186/1756-9966-29-80
  17. IARC (1994). Infection with liver flukes (Opisthorchis viverrini, Opisthorchis felineus and Clonorchis sinensis). IARC Monogr Eval Carcinog Risks Hum, 61, 121-75.
  18. Ishiguro K, Yoshida T, Yagishita H, et al (2006). Epithelial and stromal genetic instability contributes to genesis of colorectal adenomas. Gut, 55, 695-702. https://doi.org/10.1136/gut.2005.079459
  19. Iwano M, Plieth D, Danoff TM, et al (2002). Evidence that fibroblasts derive from epithelium during tissue fibrosis. J Clin Invest, 110, 341-50. https://doi.org/10.1172/JCI0215518
  20. Jezequel AM, Mancini R, Rinaldesi ML, et al (1989). Dimethylnitrosamine-induced cirrhosis. Evidence for an immunological mechanism. J Hepatol, 8, 42-52. https://doi.org/10.1016/0168-8278(89)90160-8
  21. Joyce JA, Pollard JW (2009). Microenvironmental regulation of metastasis. Nat Rev Cancer, 9, 239-52. https://doi.org/10.1038/nrc2618
  22. Kalluri R, Zeisberg M (2006). Fibroblasts in cancer. Nat Rev Cancer, 6, 392-401. https://doi.org/10.1038/nrc1877
  23. Kang JC, Chen JS, Lee CH, et al (2010). Intratumoral macrophage counts correlate with tumor progression in colorectal cancer. J Surg Oncol, 102, 242-8. https://doi.org/10.1002/jso.21617
  24. Kim S, Cho SW, Min HS, et al (2013). The expression of tumorassociated macrophages in papillary thyroid carcinoma. Endocrinol Metab (Seoul), 28, 192-8. https://doi.org/10.3803/EnM.2013.28.3.192
  25. Liu CY, Xu JY, Shi XY, et al (2013). M2-polarized tumorassociated macrophages promoted epithelial-mesenchymal transition in pancreatic cancer cells, partially through TLR4/IL-10 signaling pathway. Lab Invest, 93, 844-54. https://doi.org/10.1038/labinvest.2013.69
  26. Loilome W, Yongvanit P, Wongkham C, et al (2006). Altered gene expression in Opisthorchis viverrini-associated cholangiocarcinoma in hamster model. Mol Carcinog, 45, 279-87. https://doi.org/10.1002/mc.20094
  27. Ma J, Liu L, Che G, et al (2010). The M1 form of tumorassociated macrophages in non-small cell lung cancer is positively associated with survival time. BMC Cancer, 10, 112. https://doi.org/10.1186/1471-2407-10-112
  28. Maniecki MB, Etzerodt A, Ulhoi BP, et al (2012). Tumorpromoting macrophages induce the expression of the macrophage-specific receptor CD163 in malignant cells. Int J Cancer, 131, 2320-31. https://doi.org/10.1002/ijc.27506
  29. Mantovani A, Sica A, Sozzani S, et al (2004). The chemokine system in diverse forms of macrophage activation and polarization. Trends Immunol, 25, 677-86. https://doi.org/10.1016/j.it.2004.09.015
  30. Martinez FO, Helming L, Gordon S (2009). Alternative activation of macrophages: an immunologic functional perspective. Annu Rev Immunol, 27, 451-83. https://doi.org/10.1146/annurev.immunol.021908.132532
  31. McAnulty RJ (2007). Fibroblasts and myofibroblasts: their source, function and role in disease. Int J Biochem Cell Biol, 39, 666-71. https://doi.org/10.1016/j.biocel.2006.11.005
  32. McLean MH, Murray GI, Stewart KN, et al (2011). The inflammatory microenvironment in colorectal neoplasia. PLoS One, 6, 15366. https://doi.org/10.1371/journal.pone.0015366
  33. Medrek C, Ponten F, Jirstrom K, et al (2012). The presence of tumor associated macrophages in tumor stroma as a prognostic marker for breast cancer patients. BMC Cancer, 12, 306. https://doi.org/10.1186/1471-2407-12-306
  34. Mertens JC, Fingas CD, Christensen JD, et al (2013). Therapeutic effects of deleting cancer-associated fibroblasts in cholangiocarcinoma. Cancer Res, 73, 897-907. https://doi.org/10.1158/0008-5472.CAN-12-2130
  35. Moghaddam SJ, Li H, Cho SN, et al (2009). Promotion of lung carcinogenesis by chronic obstructive pulmonary diseaselike airway inflammation in a K-ras-induced mouse model. Am J Respir Cell Mol Biol, 40, 443-53. https://doi.org/10.1165/rcmb.2008-0198OC
  36. Nabeshima A, Matsumoto Y, Fukushi J, et al (2015). Tumourassociated macrophages correlate with poor prognosis in myxoid liposarcoma and promote cell motility and invasion via the HB-EGF-EGFR-PI3K/Akt pathways. Br J Cancer, 112, 547-55. https://doi.org/10.1038/bjc.2014.637
  37. Ni YH, Ding L, Huang XF, et al (2015). Microlocalization of CD68 tumor-associated macrophages in tumor stroma correlated with poor clinical outcomes in oral squamous cell carcinoma patients. Tumour Biol.
  38. Ohno S, Inagawa H, Dhar DK, et al (2003). The degree of macrophage infiltration into the cancer cell nest is a significant predictor of survival in gastric cancer patients. Anticancer Res, 23, 5015-22.
  39. Osterreicher CH, Penz-Osterreicher M, Grivennikov SI, et al (2011). Fibroblast-specific protein 1 identifies an inflammatory subpopulation of macrophages in the liver. Proc Natl Acad Sci U S A, 108, 308-13.
  40. Pinlaor S, Tada-Oikawa S, Hiraku Y, et al (2005). Opisthorchis viverrini antigen induces the expression of Toll-like receptor 2 in macrophage RAW cell line. Int J Parasitol, 35, 591-6. https://doi.org/10.1016/j.ijpara.2005.02.003
  41. Prakobwong S, Pinlaor S, Yongvanit P, et al (2009). Time profiles of the expression of metalloproteinases, tissue inhibitors of metalloproteases, cytokines and collagens in hamsters infected with Opisthorchis viverrini with special reference to peribiliary fibrosis and liver injury. Int J Parasitol, 39, 825-35. https://doi.org/10.1016/j.ijpara.2008.12.002
  42. Prakobwong S, Yongvanit P, Hiraku Y, et al (2010). Involvement of MMP-9 in peribiliary fibrosis and cholangiocarcinogenesis via Rac1-dependent DNA damage in a hamster model. Int J Cancer, 127, 2576-87. https://doi.org/10.1002/ijc.25266
  43. Qian BZ, Pollard JW (2010). Macrophage diversity enhances tumor progression and metastasis. Cell, 141, 39-51. https://doi.org/10.1016/j.cell.2010.03.014
  44. Rasanen K, Vaheri A (2010). Activation of fibroblasts in cancer stroma. Exp Cell Res, 316, 2713-22. https://doi.org/10.1016/j.yexcr.2010.04.032
  45. Sack U, Walther W, Scudiero D, et al (2011). S100A4-induced cell motility and metastasis is restricted by the Wnt/betacatenin pathway inhibitor calcimycin in colon cancer cells. Mol Biol Cell, 22, 3344-54. https://doi.org/10.1091/mbc.E10-09-0739
  46. Shabo I, Stal O, Olsson H, et al (2008). Breast cancer expression of CD163, a macrophage scavenger receptor, is related to early distant recurrence and reduced patient survival. Int J Cancer, 123, 780-6. https://doi.org/10.1002/ijc.23527
  47. Shaykhiev R, Bals R (2007). Interactions between epithelial cells and leukocytes in immunity and tissue homeostasis. J Leukoc Biol, 82, 1-15. https://doi.org/10.1189/jlb.0207096
  48. Sithithaworn P, Yongvanit P, Duenngai K, et al (2014). Roles of liver fluke infection as risk factor for cholangiocarcinoma. J Hepatobiliary Pancreat Sci, 21, 301-8. https://doi.org/10.1002/jhbp.62
  49. Solinas G, Germano G, Mantovani A, et al (2009). Tumorassociated macrophages (TAM) as major players of the cancer-related inflammation. J Leukoc Biol, 86, 1065-73. https://doi.org/10.1189/jlb.0609385
  50. Sripa B, Kaewkes S, Sithithaworn P, et al (2007). Liver fluke induces cholangiocarcinoma. PLoS Med, 4, 201. https://doi.org/10.1371/journal.pmed.0040201
  51. Subimerb C, Pinlaor S, Khuntikeo N, et al (2010a). Tissue invasive macrophage density is correlated with prognosis in cholangiocarcinoma. Mol Med Report, 3, 597-605.
  52. Subimerb C, Pinlaor S, Lulitanond V, et al (2010b). Circulating CD14(+) CD16(+) monocyte levels predict tissue invasive character of cholangiocarcinoma. Clin Exp Immunol, 161, 471-9. https://doi.org/10.1111/j.1365-2249.2010.04200.x
  53. Sugimoto H, Mundel TM, Kieran MW, et al (2006). Identification of fibroblast heterogeneity in the tumor microenvironment. Cancer Biol Ther, 5, 1640-6. https://doi.org/10.4161/cbt.5.12.3354
  54. Techasen A, Namwat N, Loilome W, et al (2014). Tumor necrosis factor-alpha modulates epithelial mesenchymal transition mediators ZEB2 and S100A4 to promote cholangiocarcinoma progression. J Hepatobiliary Pancreat Sci, 21, 703-11. https://doi.org/10.1002/jhbp.125
  55. Thamavit W, Bhamarapravati N, Sahaphong S, et al (1978). Effects of dimethylnitrosamine on induction of cholangiocarcinoma in Opisthorchis viverrini-infected Syrian golden hamsters. Cancer Res, 38, 4634-9.
  56. Trimboli AJ, Cantemir-Stone CZ, Li F, et al (2009). Pten in stromal fibroblasts suppresses mammary epithelial tumours. Nature, 461, 1084-91. https://doi.org/10.1038/nature08486
  57. Tsutsui S, Yasuda K, Suzuki K, et al (2005). Macrophage infiltration and its prognostic implications in breast cancer: the relationship with VEGF expression and microvessel density. Oncol Rep, 14, 425-31.
  58. Wang X, Wang H, Li G, et al (2014). Activated macrophages down-regulate expression of E-cadherin in hepatocellular carcinoma cells via NF-kappaB/Slug pathway. Tumour Biol, 35, 8893-901. https://doi.org/10.1007/s13277-014-2159-7
  59. Weber F, Shen L, Fukino K, et al (2006). Total-genome analysis of BRCA1/2-related invasive carcinomas of the breast identifies tumor stroma as potential landscaper for neoplastic initiation. Am J Hum Genet, 78, 961-72. https://doi.org/10.1086/504090
  60. Yongvanit P, Pinlaor S, Bartsch H (2012). Oxidative and nitrative DNA damage: key events in opisthorchiasis-induced carcinogenesis. Parasitol Int, 61, 130-5. https://doi.org/10.1016/j.parint.2011.06.011
  61. Yongvanit P, Pinlaor S, Loilome W (2014). Risk biomarkers for assessment and chemoprevention of liver fluke-associated cholangiocarcinoma. J Hepatobiliary Pancreat Sci, 21, 309-15. https://doi.org/10.1002/jhbp.63
  62. Zeisberg M, Yang C, Martino M, et al (2007). Fibroblasts derive from hepatocytes in liver fibrosis via epithelial to mesenchymal transition. J Biol Chem, 282, 23337-47. https://doi.org/10.1074/jbc.M700194200
  63. Zhang BC, Gao J, Wang J, et al (2011). Tumor-associated macrophages infiltration is associated with peritumoral lymphangiogenesis and poor prognosis in lung adenocarcinoma. Med Oncol, 28, 1447-52. https://doi.org/10.1007/s12032-010-9638-5
  64. Zhi K, Shen X, Zhang H, et al (2010). Cancer-associated fibroblasts are positively correlated with metastatic potential of human gastric cancers. J Exp Clin Cancer Res, 29, 66. https://doi.org/10.1186/1756-9966-29-66

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