Brief Report: Mesenchymal Stromal Cell Atrophy in Coculture Increases Aggressiveness of Transformed Cells§

Authors


  • Author contributions: M.D.C.: conception and design, collection and assembly of data, data analysis and interpretation, manuscript writing, and final approval of manuscript; L.E.L. and J.P.L.: conception and design, collection and assembly of data, data analysis and interpretation, and final approval of manuscript; A.L.: collection and assembly of data, data analysis and interpretation, and final approval of manuscript; P.H. and M.S.: financial support, administrative support, provision of study material, and final approval of manuscript; A.S.: administrative support and final approval of manuscript; M.O.L.: conception and design, financial support, administrative support, provision of study material, collection and assembly of data, data analysis and interpretation, manuscript writing, and final approval of manuscript.

  • Disclosure of potential conflicts of interest is found at the end of this article.

  • §

    first published online in STEM CELLS EXPRESS February 13, 2013.

Abstract

Mesenchymal stromal cells (MSCs) are able to influence the growth abilities of transformed cells. Here, we show that papillary thyroid cancer TPC1 and HEK 293T cells interact physically with human primary bone marrow-derived MSCs followed by evanescence of MSC cytoplasm. Interestingly, transformed cells were able to connect only to apoptotic MSCs that had lost their migration ability, whereas naïve MSCs avoided the direct contact. The interaction stimulated the proliferation of the cocultured transformed cells, activated mitogen and stress signaling, and increased resistance to cytotoxins. Consistent with in vitro data, the MSC interaction stimulated transformed cells had enhanced ability to grow and metastasize in vivo. The parental control cells showed mild tumorigenicity as compared to MSC interaction stimulated cells yielding measurable tumors in 31 days and 7 days, respectively. Our coculture model system describes how adjacent transformed cells absorb stromal cells thereby leading to the stroma-driven evolution of moderately carcinogenic cells to highly aggressive metastatic cells. STEM Cells 2013;31:1218–1223

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