BACKGROUND: The role of intratumoral tumor-associated macrophages (TAMs) in colorectal cancer (CRC) is not clear. We aim to examine the relationships of TAMs and the clinicopathologic features of CRC and the expression of matrix metalloproteinases (MMP)-2 and MMP-9. METHODS: Immunohistochemical staining of CD68, MMP-2, and MMP-9 was determined in tissue samples from CRC patients. To test the biological effect of macrophages on tumor cells, cancer cells were cocultured with macrophages and function change of cancer cells were examined. RESULTS: Intratumoral TAM count correlated with depth of invasion (P = 0.048), lymph node metastasis (P < 0.0001), and staging (P < 0.0001) of CRC. MMP-2 and MMP-9 expression was significantly associated with lymph node metastasis and staging. A significant association between intratumoral TAM counts and MMP-2 (P < 0.0001) and MMP-9 (P < 0.0001) expression was noted. When cocultured with macrophages, cancer cells increased their invasiveness and migration and elevated MMP-2 and MMP-9 secretion. CONCLUSIONS: Intratumoral TAMs cause cancer cells to have a more aggressive behavior, and this may be due to an upregulation of tumor cell-derived MMP-2 and MMP-9. Examination of intratumoral TAMs can serve as a progressive marker for CRC patients. 2010 Wiley-Liss, Inc.
BACKGROUND: The role of intratumoral tumor-associated macrophages (TAMs) in colorectal cancer (CRC) is not clear. We aim to examine the relationships of TAMs and the clinicopathologic features of CRC and the expression of matrix metalloproteinases (MMP)-2 and MMP-9. METHODS: Immunohistochemical staining of CD68, MMP-2, and MMP-9 was determined in tissue samples from CRCpatients. To test the biological effect of macrophages on tumor cells, cancer cells were cocultured with macrophages and function change of cancer cells were examined. RESULTS: Intratumoral TAM count correlated with depth of invasion (P = 0.048), lymph node metastasis (P < 0.0001), and staging (P < 0.0001) of CRC. MMP-2 and MMP-9 expression was significantly associated with lymph node metastasis and staging. A significant association between intratumoral TAM counts and MMP-2 (P < 0.0001) and MMP-9 (P < 0.0001) expression was noted. When cocultured with macrophages, cancer cells increased their invasiveness and migration and elevated MMP-2 and MMP-9 secretion. CONCLUSIONS: Intratumoral TAMs cause cancer cells to have a more aggressive behavior, and this may be due to an upregulation of tumor cell-derived MMP-2 and MMP-9. Examination of intratumoral TAMs can serve as a progressive marker for CRCpatients. 2010 Wiley-Liss, Inc.
Authors: Ines P Nearchou; Bethany M Gwyther; Elena C T Georgiakakis; Christos G Gavriel; Kate Lillard; Yoshiki Kajiwara; Hideki Ueno; David J Harrison; Peter D Caie Journal: NPJ Digit Med Date: 2020-05-15