title: Tumor associated macrophage expressing CD204 is associated with tumor aggressiveness of esophageal squamous cell carcinoma.
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.
authors: Division of Pathology, Kobe University Graduate School of Medicine, Kobe, Japan.
authors: Manabu
authors: M
authors: Shigeoka
authors: Naoki
authors: N
authors: Urakawa
authors: Tetsu
authors: T
authors: Nakamura
authors: Mari
authors: M
authors: Nishio
authors: Taketo
authors: T
authors: Watajima
authors: Daisuke
authors: D
authors: Kuroda
authors: Takahide
authors: T
authors: Komori
authors: Yoshihiro
authors: Y
authors: Kakeji
authors: Shuho
authors: S
authors: Semba
authors: Hiroshi
authors: H
authors: Yokozaki
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D002294:Carcinoma, Squamous Cell / Q000098:blood supply / Q000235:genetics* / Q000378:metabolism / Q000473:pathology*; D045744:Cell Line, Tumor; D018450:Disease Progression; D004938:Esophageal Neoplasms / Q000098:blood supply / Q000235:genetics* / Q000378:metabolism / Q000473:pathology*; D000077277:Esophageal Squamous Cell Carcinoma; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D007948:Leukemia, Monocytic, Acute / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D008207:Lymphatic Metastasis; D008264:Macrophages / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D009389:Neovascularization, Pathologic / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D011379:Prognosis; D012333:RNA, Messenger / Q000235:genetics; D051117:Scavenger Receptors, Class A / Q000096:biosynthesis* / Q000235:genetics / Q000378:metabolism; D059016:Tumor Microenvironment; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics / Q000378:metabolism
chemical_list: C495139:MSR1 protein, human; D012333:RNA, Messenger; D051117:Scavenger Receptors, Class A; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A
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