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Åke Borg

Åke Borg

Principal investigator

Åke Borg

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

Author

  • Martin Augsten
  • Christina Hagglof
  • Eleonor Olsson
  • Claudia Stolz
  • Panagiotis Tsagozis
  • Tetyana Levchenko
  • Mitchell J. Frederick
  • Åke Borg
  • Patrick Micke
  • Lars Egevad
  • Arne Ostman
Show all

Summary, in English

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.

Department/s

  • Breastcancer-genetics

Publishing year

2009

Language

English

Pages

3414-3419

Publication/Series

Proceedings of the National Academy of Sciences

Volume

106

Issue

9

Document type

Journal article

Publisher

National Academy of Sciences

Topic

  • Cancer and Oncology

Keywords

  • cancer-associated fibroblasts
  • prostate cancer
  • tumor stroma

Status

Published

ISBN/ISSN/Other

  • ISSN: 1091-6490