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2015 ; 15
(ä): 42
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Paracrine factors from adipose-mesenchymal stem cells enhance metastatic capacity
through Wnt signaling pathway in a colon cancer cell co-culture model
#MMPMID26060426
Chen D
; Liu S
; Ma H
; Liang X
; Ma H
; Yan X
; Yang B
; Wei J
; Liu X
Cancer Cell Int
2015[]; 15
(ä): 42
PMID26060426
show ga
BACKGROUND: Mesenchymal stem cells (MSCs) in tumors have emerged as progenitors
involved in stroma formation and metastasis of cancers, partially owing to their
abilities to differentially express paracrine factors related to the
proliferation and invasion of cancer cells. In this regard, increasing evidence
has shown that MSCs have impacts on the malignancy of colon cancer, however, the
underpinning mechanisms by which MSCs promote cancer metastasis remain elusive.
METHODS: To investigate the crosstalk between adipose-derived MSCs (AMSCs)
isolated from adipose tissues and colon cancer cells, a co-culture transwell
model of AMSCs and colon cancer cells was employed, and the activation of Wnt
signaling and paracrine factors in colon cancer cells and AMSCs were measured.
RESULTS: The results showed that AMSCs could enhance the metastatic capacity of
colon cancer cells with an elevated expression of mesenchymal-epithelial
transition (EMT)-associated genes in a contact-dependent manner. Reciprocally,
colon cancer cells were able to induce AMSCs to produce metastasis-related
factors and cytokines, such as FGF10, VEGFC and matrix metalloproteinases (MMPs)
in part through a mechanism of an activation of Wnt signaling, by which these
factors in turn activate Wnt signaling of colon cancer cells. Intriguingly, an
inhibition of Wnt signaling leads a reduced capacity of invasion and colony
formation of colon cancer cells in vitro, and the tumorigenicity of cancer cells
in a murine model. CONCLUSIONS: These findings thus suggest that the crosstalk
between the Wnt signaling of cancer cells and paracrine factors of AMSCs has an
implication in colon cancer malignancy. This study thus uncovers a novel
Wnt-paracrine factors mediated-crosstalk between colon cancer cells and AMSCs in
cancer malignancy.