RRC ID 44428
Author Shigeoka M, Urakawa N, Nakamura T, Nishio M, Watajima T, Kuroda D, Komori T, Kakeji Y, Semba S, Yokozaki H.
Title Tumor associated macrophage expressing CD204 is associated with tumor aggressiveness of esophageal squamous cell carcinoma.
Journal Cancer Sci.
Abstract Tumor associated macrophages (TAMs) 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 (M2) phenotype expressing CD204 and/or CD163. To know the role of TAMs in the growth and progression of esophageal squamous cell carcinomas (ESCCs), we calculated intratumoral CD204, CD163 or CD68 expressing macrophage count (MϕC) and CD34-positive microvessel density (MVD) by immunohistochemistry in 70 cases of surgically resected ESCCs and compared them with the clinicopathological factors and prognosis of patients. MϕC had positive linear association with MVD. High CD204(+) MϕC 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, CD163(+) MϕC did not associate with these clinicopathological factors with the exception of depth of tumor invasion and blood vessel invasion. Patients with high CD204(+) MϕC ESCCs showed poor disease-free survival (P = 0.021). Conditioned media of five ESCC cell lines (TE-8, -9, -10, -11 and -15) induced mRNA as well as protein expression of CD204 but not of CD163 with upregulation of vascular endothelial growth factor-A mRNA in TPA treated human acute monocytic leukemia cell line THP-1. These results overall indicate that CD204 is a useful marker for TAMs contributing to the angiogenesis, progression and prognosis of ESCCs whose specific tumor microenvironment may educate macrophages to be CD204(+) M2 TAMs.
Volume 104(8)
Pages 1112-9
Published 2013-8
DOI 10.1111/cas.12188
PMID 23648122
MeSH Aged Aged, 80 and over Carcinoma, Squamous Cell / blood supply Carcinoma, Squamous Cell / genetics* Carcinoma, Squamous Cell / metabolism Carcinoma, Squamous Cell / pathology* Cell Line, Tumor Disease Progression Esophageal Neoplasms / blood supply Esophageal Neoplasms / genetics* Esophageal Neoplasms / metabolism Esophageal Neoplasms / pathology* Esophageal Squamous Cell Carcinoma Female Humans Immunohistochemistry Leukemia, Monocytic, Acute / genetics Leukemia, Monocytic, Acute / metabolism Leukemia, Monocytic, Acute / pathology Lymphatic Metastasis Macrophages / metabolism* Male Middle Aged Neovascularization, Pathologic / genetics Neovascularization, Pathologic / metabolism Neovascularization, Pathologic / pathology Prognosis RNA, Messenger / genetics Scavenger Receptors, Class A / biosynthesis* Scavenger Receptors, Class A / genetics Scavenger Receptors, Class A / metabolism Tumor Microenvironment Vascular Endothelial Growth Factor A / genetics Vascular Endothelial Growth Factor A / metabolism
IF 4.751
Times Cited 41
Human and Animal Cells