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Suppression of PTBP1 signaling is responsible for mesenchymal stem cell induced invasion of low malignancy cancer cells.

Biochimica et biophysica acta. Molecular cell research (2018-10-18)
Xin Fu, Fangnan Xie, Fuxing Gong, Zhigang Yang, Xiaoyan Lv, Xintian Li, Hu Jiao, Qian Wang, Xia Liu, Li Yan, Ran Xiao
ABSTRAKT

Mesenchymal stem cells (MSCs) hold great promise as attractive vehicles to deliver therapeutic agents against cancer, while the cross-talk between MSCs and cancer cells remains controversial. Here in an indirect co-culture system we observed that MSCs induced the malignancy transformation of low malignancy cancer cells HT29 and MCF7, whereas MSCs were reprogrammed by high malignancy cancer cells HCT116 and MDA-MB-231 without exerting an obvious influence on them. We further demonstrated that the RNA-binding protein polypyrimidine tract-binding protein 1 (PTBP1) was suppressed in low malignancy cancer cells co-cultured with MSCs. Moreover, shRNA mediated silencing of PTBP1 could promote the invasiveness of HT29 cells while over-expression of PTBP1 attenuate the MSC-induced invasion of HT29 cells. Our results suggested that differential effects of MSCs on the invasion of cancer cells partially corresponded to PTBP1 expression in cancer cells and the maintenance of biological characteristics in MSCs, which insight could provide a theoretical basis for evaluating the safety of MSC application and PTBP1 targeting in cancer treatment.