title: Autocrine CSF-1 and CSF-1 receptor coexpression promotes renal cell carcinoma growth.
abstract: Renal cell carcinoma is increasing in incidence but the molecular mechanisms regulating its growth remain elusive. Coexpression of the monocytic growth factor colony-stimulating factor (CSF)-1 and its receptor CSF-1R on renal tubular epithelial cells (TEC) will promote proliferation and antiapoptosis during regeneration of renal tubules. Here, we show that a CSF-1-dependent autocrine pathway is also responsible for the growth of renal cell carcinoma (RCC). CSF-1 and CSF-1R were coexpressed in RCCs and TECs proximally adjacent to RCCs. CSF-1 engagement of CSF-1R promoted RCC survival and proliferation and reduced apoptosis, in support of the likelihood that CSF-1R effector signals mediate RCC growth. In vivo CSF-1R blockade using a CSF-1R tyrosine kinase inhibitor decreased RCC proliferation and macrophage infiltration in a manner associated with a dramatic reduction in tumor mass. Further mechanistic investigations linked CSF-1 and epidermal growth factor signaling in RCCs. Taken together, our results suggest that budding RCC stimulates the proximal adjacent microenvironment in the kidney to release mediators of CSF-1, CSF-1R, and epidermal growth factor expression in RCCs. Furthermore, our findings imply that targeting CSF-1/CSF-1R signaling may be therapeutically effective in RCCs.
authors: Laboratory of Molecular Autoimmune Disease, Renal Division, Brigham and Women's Hospital, Boston, Massachusetts, USA.
authors: Julia
authors: J
authors: Menke
authors: Jörg
authors: J
authors: Kriegsmann
authors: Carl Christoph
authors: CC
authors: Schimanski
authors: Melvin M
authors: MM
authors: Schwartz
authors: Andreas
authors: A
authors: Schwarting
authors: Vicki R
authors: VR
authors: Kelley
mesh_terms: D000818:Animals; D001483:Base Sequence; D002292:Carcinoma, Renal Cell / Q000378:metabolism / Q000473:pathology*; D049109:Cell Proliferation; D017931:DNA Primers; D006801:Humans; D007680:Kidney Neoplasms / Q000378:metabolism / Q000473:pathology*; D016173:Macrophage Colony-Stimulating Factor / Q000378:metabolism*; D051379:Mice; D008807:Mice, Inbred BALB C; D034622:RNA Interference; D016186:Receptor, Macrophage Colony-Stimulating Factor / Q000378:metabolism; D015398:Signal Transduction
chemical_list: D017931:DNA Primers; D016173:Macrophage Colony-Stimulating Factor; D016186:Receptor, Macrophage Colony-Stimulating Factor