Abstract 3348: Naïve rat umbilical cord matrix stem cells abrogate mammary tumor growth through markedly enhanced tumor immune responses

Abstract

Abstract Mesenchymal stem cells derived from the umbilical cord matrix (UCMSC) have great potential for therapeutic use in multiple diseases including cancer. We have demonstrated that un-engineered naïve human and rat UCMSC attenuate growth of several organ type tumors (Ayuzawa et al., Cancer Lett.2009; Ganta et al., Cancer Res, 2009, Doi et al., Cytotherapy 2010). Since UCMSC are easy to prepare in relatively large quantities and are poorly immunogenic in allogeneic transplantation, they are potentially useful in cancer therapy. However, the mechanism by which UCMSC attenuate tumor growth has not been studied rigorously. Hence, the objectives of this study were to examine the ability of UCMSC to control the growth of mammary tumors and to determine possible mechanisms by which UCMSC attenuate the tumor growth. Intratumoral injection of rat UCMSC markedly attenuated tumor growth of orthotopic Mat B III autografts in female F344 rat mammary gland. Histopathology of the tumors in the rat UCMSC group indicated that a large number of lymphocytes had infiltrated into the peritumoral area and were occasionally observed in the intratumoral area. Immunohistochemistry revealed that although CD3+ T lymphocytes were located mainly in the peritumoral area rather than in the intratumoral area, CD20+ cells were rarely seen suggesting that the majority of infiltrated lymphocytes in the rat UCMSC treated tumors were T cells. In addition, the treatment of rat UCMSC increased the CD 8+ cell infiltration throughout tumor tissue. CD68+ cells were scarcely observed in the tumors of the PBS control group but not in the rat UCMSC treated group. Transwell culture system-based in vitro migration assay revealed that rat UCMSC significantly enhanced migration of peripheral blood mononuclear cells. These results suggest that naïve rat UCMSC attenuated mammary tumor growth at least in part by markedly enhanced host immune responses against tumors. This research demonstrates that naïve rat UCMSC can be used as powerful anti-cancer therapeutic cells for breast cancer treatment. This work was supported by the Kansas State University (KSU) Terry C. Johnson Center for Basic Cancer Research, KSU CVM Dean's Fund, NIH P20 RR017686, p20 RR1556, R21CA135599 and Kansas Bioscience Authority research fund. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 3348. doi:10.1158/1538-7445.AM2011-3348