Tumor resident mesenchymal stromal cells endow naïve stromal cells with tumor-promoting properties

Oncogene. 2014 Jul 24;33(30):4016-20. doi: 10.1038/onc.2013.387. Epub 2013 Sep 30.

Abstract

Bone marrow mesenchymal stem/stromal cells (BM-MSCs) can infiltrate into tumors and subsequently evolve into tumor resident MSCs in tumor microenvironment. In this study, using a mouse lymphoma model, we showed that the lymphoma resident MSCs (L-MSCs) are able to confer tumor-promoting property to the naïve cocultured BM-MSCs. Examination of cytokines and chemokines showed that post exposure to L-MSCs, BM-MSCs acquired an expression profile that is similar to that in L-MSCs. In vivo, BM-MSCs educated by L-MSCs (BM-L-MSCs) possess a greatly enhanced ability in promoting lymphoma growth. Consistent with an elevated CCL-2 expression in BM-L-MSCs, the tumor-promoting effect of BM-L-MSCs largely depends on CCR2-mediated macrophage recruitment to tumor sites. We further showed that the transmission of tumor-promoting effect is partially mediated by soluble factors. Our findings thus revealed a novel reinforcing mechanism in the maintenance of tumor microenvironment.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Transformation, Neoplastic
  • Coculture Techniques
  • Mesenchymal Stem Cells / physiology*
  • Mice
  • Mice, Transgenic
  • Neoplasm Transplantation
  • Neoplastic Stem Cells / physiology*
  • Tumor Microenvironment