Preactivation of human MSCs with TNF- enhances tumor-suppressive activity. uri icon

abstract

  • Mesenchymal stem/stromal cells (MSCs) can either suppress or promote tumors. We found previously that incubation of human bone marrow MSCs (hMSCs) with TNF- upregulated multiple genes including TRAIL, which has cancer apoptotic activity. Here, we show that weekly infusions into mice of hMSCs preactivated with TNF- inhibited the progression of lung tumors formed from MDA-MB-231 breast cancer cells (MDA). In coculture, preactivated hMSCs induced apoptosis in MDA and several other TRAIL-sensitive cancer cell lines. TRAIL was further upregulated by apoptotic MDA cells in a TLR3-dependent manner; this feedforward cycle increased MDA cell apoptosis, and the chemotherapeutic drug doxorubicin had a synergistic effect. Also, activated hMSCs secreted DKK3 to suppress MDA cell cycling, leading to a decrease in -catenin and cyclin D1/D3 and an increase in p21. Thus, culturing hMSCs with TNF- enhances their tumor-suppressive properties and may represent a useful strategy to develop hMSC-based approaches for the treatment of cancer.

published proceedings

  • Cell Stem Cell

altmetric score

  • 9.45

author list (cited authors)

  • Lee, R. H., Yoon, N., Reneau, J. C., & Prockop, D. J.

citation count

  • 106

complete list of authors

  • Lee, Ryang Hwa||Yoon, Nara||Reneau, John C||Prockop, Darwin J

publication date

  • January 2012