CXCL14 is an autocrine growth factor for fibroblasts and acts as a multi-modal stimulator of prostate tumor growth

Forskningsoutput: TidskriftsbidragArtikel i vetenskaplig tidskrift

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 overexpressing 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.

Detaljer

Författare
  • Martin Augsten
  • Christina Hagglof
  • Eleonor Olsson
  • Claudia Stolz
  • Panagiotis Tsagozis
  • Tetyana Levchenko
  • Mitchell J. Frederick
  • Åke Borg
  • Patrick Micke
  • Lars Egevad
  • Arne Ostman
Enheter & grupper
Forskningsområden

Ämnesklassifikation (UKÄ) – OBLIGATORISK

  • Cancer och onkologi

Nyckelord

Originalspråkengelska
Sidor (från-till)3414-3419
TidskriftProceedings of the National Academy of Sciences
Volym106
Utgivningsnummer9
StatusPublished - 2009
PublikationskategoriForskning
Peer review utfördJa