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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
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 Acad Sciences

Abstract 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.

Keywords

  • Cancer and Oncology
  • cancer-associated fibroblasts
  • prostate cancer
  • tumor stroma

Other

Published
  • ISSN: 1091-6490
Åke Borg
Åke Borg
E-mail: ake [dot] borg [at] med [dot] lu [dot] se

Principal investigator

Oncology and Pathology, MV

+46 46 275 25 52

MV 404 C21B2

90

Project manager

Familial Breast Cancer

90

Professor

Oncology and Pathology, MV

MV 404 C21C2

90