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2012 ; 10
(11
): 1403-18
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Cancer-associated fibroblasts drive the progression of metastasis through both
paracrine and mechanical pressure on cancer tissue
#MMPMID23024188
Karagiannis GS
; Poutahidis T
; Erdman SE
; Kirsch R
; Riddell RH
; Diamandis EP
Mol Cancer Res
2012[Nov]; 10
(11
): 1403-18
PMID23024188
show ga
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.