CXCL14 is an autocrine growth factor for fibroblasts and acts as a multi-modal stimulator of prostate tumor growth.
Proc Natl Acad Sci U S A
; 106(9): 3414-9, 2009 Mar 03.
Article
em En
| MEDLINE
| ID: mdl-19218429
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.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Neoplasias da Próstata
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Comunicação Autócrina
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Quimiocinas CXC
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Peptídeos e Proteínas de Sinalização Intercelular
Tipo de estudo:
Prognostic_studies
Limite:
Animals
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Humans
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Male
Idioma:
En
Ano de publicação:
2009
Tipo de documento:
Article