Abstract 536: Mesenchymal stromal cells promote tumor growth both in vitro and in vivo

Abstract

Abstract [Background] Mesenchymal stromal cells (MSCs), also referred as mesenchymal stem cells are pluripotent progenitor cells that differentiate into chondrocytes, adipocytes, osteoblasts and other types of cell. Although MSCs are resident mainly in bone marrow, MSCs are found in adipose tissue, lung, and many other organs where MSCs maintain and regenerate the connective tissues of organs. Recent report proposed that MSCs also migrate and function as stromal cells in the tumor tissues. Effects of MSCs on tumor growth in vitro and in vivo are still unclear. In this study, we verified tumor promotion by MSCs and analyzed mechanisms. [Method] B16-LacZ, a melanoma cell line expressing β-galactosidase protein, was tested for their growth rate by X-gal colorizing assay in the presence or absence of mouse bone marrow MSCs in vitro. Growth of B16-LacZ was also examined in the detached condition using cell disk or conditioned medium from MSCs. Next, B16-LacZ and Lewis Lung Carcinoma (LLC) cells were mixed with MSCs at 1/1 and 1/5 ratios and subcutaneously inoculated into mice. Tumor sizes were measured and immunostaining of CD31 was performed to evaluate angiogenesis. We also determine the secretion of soluble factors associated with angiogenesis in cultured medium from B16-LacZ alone, MSCs alone, or B16-LacZ and MSCs ELISA. [Result] Proliferation of B16-LacZ co-cultured with MSCs exhibited 5.8 times greater than that of B16-LacZ alone in vitro (P<0.01). In detached condition, using cell disk or conditioned medium from MSCs, the growth rate was only 1.6 times (P<0.01) in cell disk, and 1.4 times (P<0.05) in conditioned medium at 60-hour incubation. Mixed group of B16-LacZ and MSCs at 1/1 and 1/5 ratios developed 2.3 times (P<0.05) and 4.3 times (P<0.01) grater tumor compared to B16-LacZ alone in vivo. MSCs alone did not develop a tumor. Results of LLC experiments were similar to B16-LacZ experiments. Tumor vessel area of mixture of B16-LacZ and MSCs was 2.4 times (P<0.05) at 1/1 and 4.2 times (P<0.01) at 1/5 ratio lager than B16-LacZ alone. The amount of the secretion of LIF, M-CSF, MIP-2 and VEGF factors from MSCs were significantly larger compared with B16-LacZ. The amount of the secretion from co-culture of B16-LacZ and MSCs was almost the same as the MSCs alone group. [Conclusion] MSCs promoted tumor growth both in vitro and in vivo, and promotion of tumor growth by MSCs can be at least in part attributed to the tumor angiogenesis. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 536.