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PMID: 23024188 Published · ppublish English Journal Article Review

Cancer-associated fibroblasts drive the progression of metastasis through both paracrine and mechanical pressure on cancer tissue.

Molecular cancer research : MCR ·Vol. 10 ·No. 11 ·2012-11-00 ·Pages 1403-18

Karagiannis GS, Poutahidis T, Erdman SE, Kirsch R, Riddell RH, Diamandis EP

Abstract

Neoplastic cells recruit fibroblasts through various growth factors and cytokines. These "cancer-associated fibroblasts" (CAF) actively interact with neoplastic cells and form a myofibroblastic microenvironment that promotes cancer growth and survival and supports malignancy. Several products of their paracrine signaling repertoire have been recognized as tumor growth and metastasis regulators. However, tumor-promoting cell signaling is not the only reason that makes CAFs key components of the "tumor microenvironment," as CAFs affect both the architecture and growth mechanics of the developing tumor. CAFs participate in the remodeling of peritumoral stroma, which is a prerequisite of neoplastic cell invasion, expansion, and metastasis. CAFs are not present peritumorally as individual cells but they act orchestrated to fully deploy a desmoplastic program, characterized by "syncytial" (or collective) configuration and altered cell adhesion properties. Such myofibroblastic cohorts are reminiscent of those encountered in wound-healing processes. The view of "cancer as a wound that does not heal" led to useful comparisons between wound healing and tumorigenesis and expanded our knowledge of the role of CAF cohorts in cancer. In this integrative model of cancer invasion and metastasis, we propose that the CAF-supported microenvironment has a dual tumor-promoting role. Not only does it provide essential signals for cancer cell dedifferentiation, proliferation, and survival but it also facilitates cancer cell local invasion and metastatic phenomena.

MeSH Terms
Disease Progression Fibroblasts/metabolism,pathology Humans Neoplasm Metastasis Neoplasms/metabolism,pathology Paracrine Communication Tumor Microenvironment
Authors & Affiliations
6 authors, click to expand affiliations / ORCID
Karagiannis George S
Department of Laboratory Medicine and Pathobiology, University of Toronto, Canada.
Poutahidis Theofilos
Erdman Susan E
Kirsch Richard
Riddell Robert H
Diamandis Eleftherios P
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Article Info
Journal
Molecular cancer research : MCR
Abbr.
Mol Cancer Res
ISSN
1557-3125
DOI
10.1158/1541-7786.MCR-12-0307
Published
2012-11-00
Epub
2012-00-28
Pages
1403-18
Language
English
Region
United States
NLM ID
101150042
PMCID
PMC4399759
Subset
IM
Grants
NIEHS NIH HHS · P30 ES002109 · United States
External Links
PubMed source DOI: 10.1158/1541-7786.MCR-12-0307 PMC Full Text View journal details
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