title: Macrophage infiltration and its prognostic relevance in clear cell renal cell carcinoma.
abstract: Most malignant tumors evidence infiltration of many macrophages. In this study, we investigated an anti-inflammatory macrophage phenotype (M2) in clear cell renal cell carcinoma (RCC) using CD163 and CD204 as markers. Immunostaining showed a correlation between the number of CD163(+) cells and age, sex, nuclear grade, and TNM classification. High infiltration of CD163(+) cells was significantly associated with poor clinical prognosis in univariate analysis but not in multivariate analysis. We also carried out in vitro studies to examine cell-cell interactions between macrophages and cancer cells. Culture supernatants from RCC cell lines induced polarization of macrophages toward the M2 phenotype. Coculture of macrophages with cancer cells significantly induced activation of signal transducers and activators of transcription-3 (Stat3) in the cancer cells. Direct coculture of RCC cells with macrophages led to stronger activation of Stat3 in the cancer cells than did indirect coculture using Transwell chamber dishes. Because RCC cells expressed membrane-type macrophage colony-stimulating factor (mM-CSF) on the cell surface, we suggested that this mM-CSF plays an important role in direct cell-cell interactions. Stat3 activation in cancer cells that was induced by coculture with macrophages was suppressed by downregulation of the M-CSF receptor (M-CSFR) in macrophages and by an inhibitor of M-CSFR. In conclusion, investigation of CD163(+) tumor-associated macrophages would be useful for assessment of the clinical prognosis of patients with ccRCC. Cell-cell interactions mediated by mM-CSF and M-CSFR binding could contribute to cancer cell activation.
authors: Department of Cell Pathology, Graduate School of Medical Sciences, Kumamoto University, Kumamoto, Japan.
authors: Yoshihiro
authors: Y
authors: Komohara
authors: Horlad
authors: H
authors: Hasita
authors: Koji
authors: K
authors: Ohnishi
authors: Yukio
authors: Y
authors: Fujiwara
authors: Shinya
authors: S
authors: Suzu
authors: Masatoshi
authors: M
authors: Eto
authors: Motohiro
authors: M
authors: Takeya
mesh_terms: D000328:Adult; D000368:Aged; D015703:Antigens, CD / Q000032:analysis; D015214:Antigens, Differentiation, Myelomonocytic / Q000032:analysis; D002292:Carcinoma, Renal Cell / Q000401:mortality / Q000473:pathology*; D002450:Cell Communication; D002454:Cell Differentiation; D045744:Cell Line, Tumor; D005260:Female; D006801:Humans; D007680:Kidney Neoplasms / Q000401:mortality / Q000473:pathology*; D016173:Macrophage Colony-Stimulating Factor / Q000502:physiology; D008264:Macrophages / Q000737:chemistry / Q000502:physiology*; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D016016:Proportional Hazards Models; D011956:Receptors, Cell Surface / Q000032:analysis; D050796:STAT3 Transcription Factor / Q000378:metabolism; D051117:Scavenger Receptors, Class A / Q000032:analysis; D000098902:CD163 Antigen
chemical_list: D015703:Antigens, CD; D015214:Antigens, Differentiation, Myelomonocytic; D000098902:CD163 Antigen; C495139:MSR1 protein, human; D011956:Receptors, Cell Surface; D050796:STAT3 Transcription Factor; C494086:STAT3 protein, human; D051117:Scavenger Receptors, Class A; D016173:Macrophage Colony-Stimulating Factor