CXCL14 is an autocrine growth factor for fibroblasts and acts as a multi-modal stimulator of prostate tumor growth
Research output: Contribution to journal › Research article › Contributed › peer-review
Contributors
Abstract
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.
Details
Original language | English |
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Pages (from-to) | 3414-9 |
Number of pages | 6 |
Journal | Proceedings of the National Academy of Sciences of the United States of America : PNAS |
Volume | 106 |
Issue number | 9 |
Publication status | Published - 3 Mar 2009 |
Peer-reviewed | Yes |
External IDs
PubMedCentral | PMC2651265 |
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Scopus | 60949112215 |
ORCID | /0000-0002-5247-908X/work/142241947 |
Keywords
Research priority areas of TU Dresden
Sustainable Development Goals
Keywords
- Animals, Autocrine Communication, Cell Line, Tumor, Cell Movement, Cell Proliferation, Chemokines, CXC/genetics, Epithelial Cells/cytology, Fibroblasts, Humans, Intercellular Signaling Peptides and Proteins/metabolism, Macrophages, Male, Mice, Neovascularization, Pathologic/genetics, Prostatic Neoplasms/genetics, Stromal Cells/cytology, Up-Regulation, Xenograft Model Antitumor Assays