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

Biochim Biophys Acta Mol Cell Res. 2018 Nov;1865(11 Pt A):1552-1565. doi: 10.1016/j.bbamcr.2018.08.002. Epub 2018 Aug 9.

Abstract

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.

Keywords: Different malignancy cancer cells; Indirect co-culture; Invasiveness; Mesenchymal stem cells; PTBP1.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Line, Tumor
  • Cell Movement
  • Cell Proliferation
  • Coculture Techniques
  • Female
  • Gene Expression
  • Gene Silencing
  • HCT116 Cells
  • HT29 Cells
  • Heterogeneous-Nuclear Ribonucleoproteins / genetics
  • Heterogeneous-Nuclear Ribonucleoproteins / metabolism*
  • Humans
  • Interferon Type I / metabolism
  • Mesenchymal Stem Cells / metabolism*
  • Mice
  • Paracrine Communication
  • Polypyrimidine Tract-Binding Protein / genetics
  • Polypyrimidine Tract-Binding Protein / metabolism*
  • RNA, Small Interfering / genetics
  • STAT1 Transcription Factor
  • Signal Transduction*

Substances

  • Heterogeneous-Nuclear Ribonucleoproteins
  • Interferon Type I
  • PTBP1 protein, human
  • RNA, Small Interfering
  • STAT1 Transcription Factor
  • STAT1 protein, human
  • Polypyrimidine Tract-Binding Protein