Intratumoral macrophage counts correlate with tumor progression in colorectal cancer

Abstract

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 ¼ 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 cellderived MMP-2 and MMP-9. Examination of intratumoral TAMs can serve as a progressive marker for CRC patients.

Immune Cells in Colorectal Cancer: Prognostic Relevance and Role of MSI

“…In contrast, intratumoral TAMs count has been correlated with depth of invasion, lymph node metastasis, and staging of CRC, suggesting that intratumoral macrophages cause cancer cells to have a more aggressive behavior [24,25].…”

Urotensin II contributes to the formation of lung adenocarcinoma inflammatory microenvironment through the NF-κB pathway in tumor-bearing nude mice

“…There are numerous types of inflammatory cells in the tumor microenvironment, and tumor-associated macrophages (TAMs) are a major component. While the role of TAMs in tumor development is complex and multifaceted, in clinical studies, increased TAM density has been found to be associated with poor prognosis (5)(6)(7). TAMs contribute to tumor development through several mechanisms, including releasing angiogenic factors, promoting tumor cell proliferation, and facilitating tumor cell invasion and metastasis (8).…”

“…TAMs, in particular, have been found to be associated with tumor growth and metastasis (5)(6)(7). A large number of studies concerning numerous tumor types, including colorectal cancer (5), supraglottic laryngeal carcinoma (6), Ewing's sarcoma (7), intestinal type gastric cancer (29), pancreatic cancer (30), non-gynecologic leiomyosarcoma (31) and thyroid cancer (32), have shown that the presence of TAMs in the tumor microenvironment is associated with a worse prognosis.…”

A novel gene expression signature in peripheral blood mononuclear cells for early detection of colorectal cancer

“…43 Tumour-associated macrophages (TAM), whose presence is strongly associated with CRC progression, are the main source of MMP9 in the tumour microenvironment. 44 Of interest, we previously reported elevated levels of circulating MMP-9 in the blood of CRC patients. 45 MMP-9 up-regulation alone, however, is not specific to CRC, as it has also been reported in other malignant tumours and in autoimmune or inflammatory diseases, including ulcerative colitis or lymphocytic colitis.…”