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CXCL14 is an autocrine growth factor for fibroblasts and acts as a multi-modal stimulator of prostate tumor growth
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CXCL14 is an autocrine growth factor for fibroblasts and acts as a multi-modal stimulator of prostate tumor growth
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Journal Article
CXCL14 is an autocrine growth factor for fibroblasts and acts as a multi-modal stimulator of prostate tumor growth
2009
Overview
This study explored the role of secreted fibroblast-derived factors in prostate cancer growth. Analyses of matched normal and tumor tissue revealed up-regulation of CXCL14 in cancer-associated fibroblasts of a majority of prostate cancer. Fibroblasts over-expressing CXCL14 promoted the growth of prostate cancer xenografts, and increased tumor angiogenesis and macrophage infiltration. Mechanistic studies demonstrated that autocrine CXCL14-stimulation of fibroblasts stimulate migration and ERK-dependent proliferation of fibroblasts. CXCL14-stimulation of monocyte migration was also demonstrated. Furthermore, CXCL14-producing fibroblasts, but not recombinant CXCL14, enhanced in vitro proliferation and migration of prostate cancer cells and in vivo angiogenesis. These studies thus identify CXCL14 as a novel autocrine stimulator of fibroblast growth and migration, with multi-modal tumor-stimulatory activities. In more general terms, our findings suggest autocrine stimulation of fibroblasts as a previously unrecognized mechanism for chemokine-mediated stimulation of tumor growth, and suggest a novel mechanism whereby cancer-associated fibroblasts achieve their pro-tumorigenic phenotype.
Publisher
National Academy of Sciences,National Acad Sciences
Subject
/ Animals
/ Cancer
/ cancer-associated fibroblasts
/ Chemokines, CXC - metabolism
/ CXCL14
/ Epithelial Cells - metabolism
/ Humans
/ Intercellular Signaling Peptides and Proteins - metabolism
/ Intercellular Signaling Peptides and Proteins - secretion
/ Kirurgi
/ Male
/ MEDICIN
/ MEDICINE
/ Mice
/ Morfologi, cellbiologi, patologi
/ Morphology, cell biology, pathology
/ Neovascularization, Pathologic - genetics
/ Neovascularization, Pathologic - metabolism
/ Patologi
/ Prostatic Neoplasms - genetics
/ Prostatic Neoplasms - metabolism
/ Prostatic Neoplasms - pathology
/ Prostatic Neoplasms - secretion
/ Surgery
/ Tissues
/ Tumors
