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

Research output: Contribution to journalArticle

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.

Details

Authors
  • Martin Augsten
  • Christina Hagglof
  • Eleonor Olsson
  • Claudia Stolz
  • Panagiotis Tsagozis
  • Tetyana Levchenko
  • Mitchell J. Frederick
  • Åke Borg
  • Patrick Micke
  • Lars Egevad
  • Arne Ostman
Organisations
Research areas and keywords

Subject classification (UKÄ) – MANDATORY

  • Cancer and Oncology

Keywords

  • cancer-associated fibroblasts, prostate cancer, tumor stroma
Original languageEnglish
Pages (from-to)3414-3419
JournalProceedings of the National Academy of Sciences
Volume106
Issue number9
Publication statusPublished - 2009
Publication categoryResearch
Peer-reviewedYes