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Correlations of Tumor-associated Macrophage Subtypes with Liver Metastases of Colorectal Cancer

  • Cui, Yun-Long (Department of Hepatobiliary Surgery, Tianjin Medical University Cancer Institute and Hospital) ;
  • Li, Hui-Kai (Department of Hepatobiliary Surgery, Tianjin Medical University Cancer Institute and Hospital) ;
  • Zhou, Hong-Yuan (Department of Hepatobiliary Surgery, Tianjin Medical University Cancer Institute and Hospital) ;
  • Zhang, Ti (Department of Hepatobiliary Surgery, Tianjin Medical University Cancer Institute and Hospital) ;
  • Li, Qiang (Department of Hepatobiliary Surgery, Tianjin Medical University Cancer Institute and Hospital)
  • Published : 2013.02.28

Abstract

Objective: This work aimed to investigate the correlations of tumor-associated macrophages (TAMs) and their subtypes M1 and M2 with liver metastasis of colorectal cancer, and provide useful references for seeking predictors of liver metastasis and studying mechanisms. Methods: 120 patients with colorectal cancer from 2000 to 2009 were divided into low, middle and high liver metastasis groups (group A, B and C, respectively). S-P immunohistochemical staining and microscopic observation were conducted to compare expression in CD68-positive cells (TAMs), CD80-positive cells (M1) and CD163-positive cells (M2) in three groups. Correlations of TAMs, M1, M2, and M2/M1 ratio with clinical and pathological parameters were analyzed. Results: With increase of liver metastatic ability, the number of TAMs decreased gradually, with no significant difference between any two of the three groups (P > 0.05), while the numbers of M1 and M2 were significantly decreased and increased, respectively, with significant difference between any two of three groups (P < 0.05 or P < 0.01). In addition, the M2/M1 ratio increased with increase of liver metastatic ability (P < 0.01). There was no statistical significance of correlation of TAMs with each clinical and pathological parameter. M1 was negatively related with lymphatic metastasis and liver metastatic ability. M2 was positively correlated with preoperative CEA level, lymphatic metastasis, tumor differentiation degree and liver metastatic ability. The same was the case for the M2/M1 ratio. Conclusions: Effects of TAMs on liver metastasis of colorectal cancer do not depend on the total number of TAMs, but on the number and proportion of functional subtypes M1 and M2. M2 number and M2/M1 ratio are more accurate predictors for liver metastasis of colorectal cancer.

Keywords

References

  1. Aarons CB, Bajenova O, Andrews C, et al (2007). Carcinoembryonic antigen-stimulated THP-1 macrophages activate endothelial cells and increase cell-cell adhesion of colorectal cancer cells. Clin Exp Metastasis, 24, 201-9. https://doi.org/10.1007/s10585-007-9069-7
  2. Adachi Y, Inomata M, Kakisako K, et al (1999). Histopathologic characteristics of colorectal cancer with liver metastasis. Dis Colon Rectum, 42, 1053-6. https://doi.org/10.1007/BF02236702
  3. Algars A, Irjala H, Vaittinen S, et al (2012). Type and location of tumor-infiltrating macrophages and lymphatic vessels predict survival of colorectal cancer patients. Int J Cancer, 131, 864-73. https://doi.org/10.1002/ijc.26457
  4. Coussens LM, Werb Z (2002). Inflammation and cancer. Nature, 420, 860-7. https://doi.org/10.1038/nature01322
  5. Green CE, Liu T, Montel V, et al (2009). Chemoattractant signaling between tumor cells and macrophages regulates cancer cell migration, metastasis and neovascularization. PLoS One, 4, e6713. https://doi.org/10.1371/journal.pone.0006713
  6. Hatate K, Yamashita K, Hirai K, et al (2008). Liver metastasis of colorectal cancer by protein-tyrosine phosphatase type 4A, 3 (PRL-3) is mediated through lymph node metastasis and elevated serum tumor markers such as CEA and CA19-9. Oncol Rep, 20, 737-43.
  7. Hu H, Sun L, Guo C, et al (2009). Tumor cell-microenvironment interaction models coupled with clinical validation reveal CCL2 and SNCG as two predictors of colorectal cancer hepatic metastasis. Clin Cancer Res, 15, 5485-93. https://doi.org/10.1158/1078-0432.CCR-08-2491
  8. Imano M, Okuno K, Itoh T, et al (2011). Osteopontin induced by macrophages contribute to metachronous liver metastases in colorectal cancer. Am Surg, 77, 1515-20.
  9. Jedinak A, Dudhgaonkar S, Sliva D (2010). Activated macrophages induce metastatic behavior of colon cancer cells. Immunobiology, 215, 242-9. https://doi.org/10.1016/j.imbio.2009.03.004
  10. Kemeny N (2006). Management of liver metastases from colorectal cancer. Oncology (Williston Park), 20, 1161-80, 1185-6.
  11. Kinouchi M, Miura K, Mizoi T, et al (2011). Infiltration of CD14-positive macrophages at the invasive front indicates a favorable prognosis in colorectal cancer patients with lymph node metastasis. Hepatogastroenterology, 58, 352-8.
  12. Leek RD, Lewis CE, Whitehouse R, et al (1996). Association of macrophage infiltration with angiogenesis and prognosis in invasive breast carcinoma. Cancer Res, 56, 4625-9.
  13. Leskoviku S, Lasku A, Marku N, Rada F, Dibra A (1992). Usefulness of the determination of carcinoembryonic antigen (CEA) in the serum of patients with colorectal cancer in Albania. Panminerva Med, 34, 168-71.
  14. Ma J, Liu L, Che G, et al (2010). The M1 form of tumor-associated 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
  15. Ong SM, Tan YC, Beretta O, et al (2012). Macrophages in human colorectal cancer are pro-inflammatory and prime T cells towards an anti-tumour type-1 inflammatory response. Eur J Immunol, 42, 89-100. https://doi.org/10.1002/eji.201141825
  16. Pander J, Heusinkveld M, van der Straaten T, et al (2011). Activation of tumor-promoting type 2 macrophages by EGFR-targeting antibody cetuximab. Clin Cancer Res, 17, 5668-73. https://doi.org/10.1158/1078-0432.CCR-11-0239
  17. Parkin DM, Bray F, Ferlay J, Pisani P (2005). Global cancer statistics, 2002. CA Cancer J Clin, 55, 74-108. https://doi.org/10.3322/canjclin.55.2.74
  18. Penna C, Nordlinger B (2002). Colorectal metastasis (liver and lung). Surg Clin North Am, 82, 1075-90. https://doi.org/10.1016/S0039-6109(02)00051-8
  19. Rolny C, Mazzone M, Tugues S, et al (2011). HRG Inhibits Tumor Growth and Metastasis by Inducing Macrophage Polarization and Vessel Normalization through Downregulation of PlGF. Cancer Cell, 19, 31-44. https://doi.org/10.1016/j.ccr.2010.11.009
  20. Takai H, Ashihara M, Ishiguro T, et al (2009). Involvement of glypican-3 in the recruitment of M2-polarized tumor-associated macrophages in hepatocellular carcinoma. Cancer Biol Ther, 8, 2329-38.
  21. Talbot IC, Ritchie S, Leighton MH, et al (1980). The clinical significance of invasion of veins by rectal cancer. Br J Surg, 67, 439-42. https://doi.org/10.1002/bjs.1800670619
  22. Thomas P, Gangopadhyay A, Steele G Jr, et al (1995). The effect of transfection of the CEA gene on the metastatic behavior of the human colorectal cancer cell line MIP-101. Cancer Lett, 92, 59-66. https://doi.org/10.1016/0304-3835(95)03764-N
  23. Wong SK, Jalaludin BB, Henderson CJ, et al (2008). Direct tumor invasion in colon cancer: correlation with tumor spread and survival. Dis Colon Rectum, 51, 1331-8. https://doi.org/10.1007/s10350-008-9274-8
  24. Zhou Q, Peng RQ, Wu XJ, et al (2010). The density of macrophages in the invasive front is inversely correlated to liver metastasis in colon cancer. J Transl Med, 8, 13. https://doi.org/10.1186/1479-5876-8-13

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