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.
©2013 AACR.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Bone Morphogenetic Protein 6 / genetics
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Bone Morphogenetic Protein 6 / metabolism*
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Carcinoma, Renal Cell / metabolism*
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Carcinoma, Renal Cell / pathology
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Cell Line
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Cell Line, Tumor
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Cell Proliferation / drug effects
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Clodronic Acid / pharmacology
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Doxycycline / pharmacology
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Humans
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Immunoblotting
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Interleukin-10 / genetics
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Interleukin-10 / metabolism*
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Kaplan-Meier Estimate
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Kidney Neoplasms / metabolism*
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Kidney Neoplasms / pathology
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Macrophages / drug effects
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Macrophages / metabolism*
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Mice
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Mice, Inbred BALB C
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Mice, Knockout
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Microscopy, Fluorescence
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RNA Interference
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Reverse Transcriptase Polymerase Chain Reaction
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STAT3 Transcription Factor / genetics
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STAT3 Transcription Factor / metabolism
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Smad5 Protein / genetics
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Smad5 Protein / metabolism
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Tumor Burden / drug effects
Substances
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Bone Morphogenetic Protein 6
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STAT3 Transcription Factor
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Smad5 Protein
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Clodronic Acid
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Interleukin-10
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Doxycycline