Adipose-Derived Stem Cells Facilitate Ovarian Tumor Growth and Metastasis by Promoting Epithelial to Mesenchymal Transition Through Activating the TGF-β Pathway

Adipose-derived stem cells (ADSC) are multipotent mesenchymal stem cells derived from adipose tissues and are capable of differentiating into multiple cell types in the tumor microenvironment (TME). The roles of ADSC in ovarian cancer (OC) metastasis are still not well defined. To understand whether ADSC contributes to ovarian tumor metastasis, we examined epithelial to mesenchymal transition (EMT) markers in OC cells following the treatment of the ADSC-conditioned medium (ADSC-CM). ADSC-CM promotes EMT in OC cells. Functionally, ADSC-CM promotes OC cell proliferation, survival, migration, and invasion. We further demonstrated that ADSC-CM induced EMT via TGF-beta growth factor secretion from ADSC and the ensuing activation of the TGF-beta pathway. ADSC-CM-induced EMT in OC cells was reversible by the TGF-beta inhibitor SB431542 treatment. Using an orthotopic OC mouse model, we also provide the experimental evidence that ADSC contributes to ovarian tumor growth and metastasis by promoting EMT through activating the TGF-beta pathway. Taken together, our data indicate that targeting ADSC using the TGF-beta inhibitor has the therapeutic potential in blocking the EMT and OC metastasis.

Automated summary

Adipose-derived stem cells (ADSC) play a promoting role in ovarian cancer metastasis by inducing epithelial to mesenchymal transition (EMT) in OC cells, leading to proliferation, survival, migration, and invasion. Experimental evidence shows that ADSC contributes to ovarian tumor growth and metastasis by activating the TGF-beta pathway. Targeting ADSC with TGF-beta inhibitor has therapeutic potential in blocking EMT and OC metastasis.