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

Augsten, Martin; Hagglof, Christina; Olsson, Eleonor LU ; Stolz, Claudia; Tsagozis, Panagiotis; Levchenko, Tetyana; Frederick, Mitchell J.; Borg, Åke LU ; Micke, Patrick and Egevad, Lars, et al. (2009) In Proceedings of the National Academy of Sciences 106(9). p.3414-3419
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... (More)
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. (Less)
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publication status
published
subject
keywords
cancer-associated fibroblasts, prostate cancer, tumor stroma
in
Proceedings of the National Academy of Sciences
volume
106
issue
9
pages
3414 - 3419
publisher
National Acad Sciences
external identifiers
  • wos:000263844100078
  • scopus:60949112215
ISSN
1091-6490
DOI
10.1073/pnas.0813144106
language
English
LU publication?
yes
id
ec079ddb-a645-4aaa-9841-18cd2c6c287c (old id 1370603)
date added to LUP
2009-05-08 13:23:22
date last changed
2017-12-03 03:21:18
@article{ec079ddb-a645-4aaa-9841-18cd2c6c287c,
  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.},
  author       = {Augsten, Martin and Hagglof, Christina and Olsson, Eleonor and Stolz, Claudia and Tsagozis, Panagiotis and Levchenko, Tetyana and Frederick, Mitchell J. and Borg, Åke and Micke, Patrick and Egevad, Lars and Ostman, Arne},
  issn         = {1091-6490},
  keyword      = {cancer-associated fibroblasts,prostate cancer,tumor stroma},
  language     = {eng},
  number       = {9},
  pages        = {3414--3419},
  publisher    = {National Acad Sciences},
  series       = {Proceedings of the National Academy of Sciences},
  title        = {CXCL14 is an autocrine growth factor for fibroblasts and acts as a multi-modal stimulator of prostate tumor growth},
  url          = {http://dx.doi.org/10.1073/pnas.0813144106},
  volume       = {106},
  year         = {2009},
}