title: BMP-6 in renal cell carcinoma promotes tumor proliferation through IL-10-dependent M2 polarization of tumor-associated macrophages.
abstract: Dysregulated bone morphogenetic proteins (BMP) may contribute to the development and progression of renal cell carcinoma (RCC). Herein, we report that BMP-6 promotes the growth of RCC by interleukin (IL)-10-mediated M2 polarization of tumor-associated macrophages (TAM). BMP-6-mediated IL-10 expression in macrophages required Smad5 and STAT3. In human RCC specimens, the three-marker signature BMP-6/IL-10/CD68 was associated with a poor prognosis. Furthermore, patients with elevated IL-10 serum levels had worse outcome after surgery. Together, our results suggest that BMP-6/macrophage/IL-10 regulates M2 polarization of TAMs in RCC.
authors: Section of Urologic Oncology, The Cancer Institute of New Jersey and Robert Wood Johnson Medical School, New Brunswick, NJ 08903, USA.
authors: Jae-Ho
authors: JH
authors: Lee
authors: Geun Taek
authors: GT
authors: Lee
authors: Seung Hyo
authors: SH
authors: Woo
authors: Yun-Sok
authors: YS
authors: Ha
authors: Seok Joo
authors: SJ
authors: Kwon
authors: Wun-Jae
authors: WJ
authors: Kim
authors: Isaac Yi
authors: IY
authors: Kim
mesh_terms: D000818:Animals; D055418:Bone Morphogenetic Protein 6 / Q000235:genetics / Q000378:metabolism*; D002292:Carcinoma, Renal Cell / Q000378:metabolism* / Q000473:pathology; D002460:Cell Line; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D004002:Clodronic Acid / Q000494:pharmacology; D004318:Doxycycline / Q000494:pharmacology; D006801:Humans; D015151:Immunoblotting; D016753:Interleukin-10 / Q000235:genetics / Q000378:metabolism*; D053208:Kaplan-Meier Estimate; D007680:Kidney Neoplasms / Q000378:metabolism* / Q000473:pathology; D008264:Macrophages / Q000187:drug effects / Q000378:metabolism*; D051379:Mice; D008807:Mice, Inbred BALB C; D018345:Mice, Knockout; D008856:Microscopy, Fluorescence; D034622:RNA Interference; D020133:Reverse Transcriptase Polymerase Chain Reaction; D050796:STAT3 Transcription Factor / Q000235:genetics / Q000378:metabolism; D051902:Smad5 Protein / Q000235:genetics / Q000378:metabolism; D047368:Tumor Burden / Q000187:drug effects
chemical_list: D055418:Bone Morphogenetic Protein 6; D050796:STAT3 Transcription Factor; D051902:Smad5 Protein; D004002:Clodronic Acid; D016753:Interleukin-10; D004318:Doxycycline