The Role of Mesenchymal Stem Cells in Promoting Ovarian Cancer Growth and Spread PRINCIPAL INVESTIGATOR :

Background: Currently, there are many promising clinical trials using mesenchymal stem cells (MSCs) in cell-based therapies of numerous diseases. Increasingly, however, there is a concern over the use of MSCs because they home to tumors and can support tumor growth and metastasis. For instance, we established that MSCs in the ovarian tumor microenvironment promoted tumor growth and favored angiogenesis. In parallel studies, we also developed a new approach to induce the conventional mixed pool of MSCs into two uniform but distinct phenotypes we termed MSC1 and MSC2. Methodology/Principal Findings: Here we tested the in vitro and in vivo stability of MSC1 and MSC2 phenotypes as well as their effects on tumor growth and spread. In vitro co-culture of MSC1 with various cancer cells diminished growth in colony forming units and tumor spheroid assays, while conventional MSCs or MSC2 co-culture had the opposite effect in these assays. Co-culture of MSC1 and cancer cells also distinctly affected their migration and invasion potential when compared to MSCs or MSC2 treated samples. The expression of bioactive molecules also differed dramatically among these samples. MSC1-based treatment of established tumors in an immune competent model attenuated tumor growth and metastasis in contrast to MSCsand MSC2-treated animals in which tumor growth and spread was increased. Also, in contrast to these groups, MSC1-therapy led to less ascites accumulation, increased CD45+leukocytes, decreased collagen deposition, and mast cell degranulation. Conclusion/Significance: These observations indicate that the MSC1 and MSC2 phenotypes may be convenient tools for the discovery of critical components of the tumor stroma. The continued investigation of these cells may help ensure that cell based-therapy is used safely and effectively in human disease. Citation: Waterman RS, Henkle SL, Betancourt AM (2012) Mesenchymal Stem Cell 1 (MSC1)-Based Therapy Attenuates Tumor Growth Whereas MSC2-Treatment Promotes Tumor Growth and Metastasis. PLoS ONE 7(9): e45590. doi:10.1371/journal.pone. 0045590 Editor: Paolo Fiorina, Children’s Hospital Boston/Harvard Medical School, United States of America Received April 24, 2012; Accepted August 23, 2012; Published September 20, 2012 Copyright: 2012 Waterman et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Funding: Funding was provided to AMB by the National Institutes of Health 1P20RR20152-01, Department of Defense OC073102 Concept Award and research support from the Tulane Cancer Center and the Center for Stem Cell Research and Regenerative Medicine. Funding was provided to RSW by the Foundation for Anesthesiology Education and Research (FAER). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. No additional external funding was received for this study. Competing Interests: Aline M. Betancourt is the inventor of the patent-pending ‘‘Mesenchymal Stem Cells and Related Therapies’’ (MSC1 and MSC2 methodology) US 61/391,749. Aline M. Betancourt is Founder and Chief Financial Officer for wibi+works, LLC without any salary, benefit or income. As inventor of the patent stated above there are no interests, products, benefits, compensations, or salary. Ruth S. Waterman is the Chief Executive Officer for wibi+works, LLC without any benefit, salary, or income. There are no further patents, products in development or marketed products to declare. This does not alter the authors’ adherence to all the PLOS ONE policies on sharing data and materials. * E-mail: alibscan@tulane.edu