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-α upregulated multiple genes including TRAIL, which has cancer apoptotic activity. Here, we show that weekly infusions into mice of hMSCs preactivated with TNF-α 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 β-catenin and cyclin D1/D3 and an increase in p21. Thus, culturing hMSCs with TNF-α enhances their tumor-suppressive properties and may represent a useful strategy to develop hMSC-based approaches for the treatment of cancer.
journal_name
Cell Stem Celljournal_title
Cell stem cellauthors
Lee RH,Yoon N,Reneau JC,Prockop DJdoi
10.1016/j.stem.2012.10.001subject
Has Abstractpub_date
2012-12-07 00:00:00pages
825-35issue
6eissn
1934-5909issn
1875-9777pii
S1934-5909(12)00581-4journal_volume
11pub_type
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