Tumor associated macrophage expressing CD 204 is associated with tumor aggressiveness of esophageal squamous cell carcinoma

Abstract

Tumor associated macrophages (TAM s) are the most abundant cancer stromal cells educated by tumor microenvironment to acquire trophic functions facilitating angiogenesis, matrix breakdown and cancer cell motility. Tumor associated macrophages have anti‐inflammatory properties or “alternatively” activated (M 2) phenotype expressing CD 204 and/or CD 163. To know the role of TAM s in the growth and progression of esophageal squamous cell carcinomas (ESCC s), we calculated intratumoral CD 204, CD 163 or CD 68 expressing macrophage count (M ϕ C) and CD 34‐positive microvessel density (MVD) by immunohistochemistry in 70 cases of surgically resected ESCC s and compared them with the clinicopathological factors and prognosis of patients. M ϕ C had positive linear association with MVD. High CD 204+ M ϕ C were significantly correlated with more malignant phenotypes including depth of tumor invasion, lymph and blood vessel invasion, lymph node metastasis as well as clinical stages. On the other hand, CD 163+ M ϕ C did not associate with these clinicopathological factors with the exception of depth of tumor invasion and blood vessel invasion. Patients with high CD 204+ M ϕ C ESCC s showed poor disease‐free survival (P = 0.021). Conditioned media of five ESCC cell lines (TE‐8, ‐9, ‐10, ‐11 and ‐15) induced m RNA as well as protein expression of CD 204 but not of CD 163 with upregulation of vascular endothelial growth factor‐A m RNA in TPA treated human acute monocytic leukemia cell line THP‐1. These results overall indicate that CD 204 is a useful marker for TAM s contributing to the angiogenesis, progression and prognosis of ESCC s whose specific tumor microenvironment may educate macrophages to be CD 204+ M 2 TAM s.