Data from Niche-Dependent Tumorigenic Capacity of Malignant Ovarian Ascites-Derived Cancer Cell Subpopulations

Abstract

<div>Abstract<p><b>Purpose:</b> In previous studies, we have used human embryonic stem cells (hESC) to generate a tissue microenvironment in immunocompromised mice as an experimental approach for studying human tumorigenesis. We now examine the attributes of such a cellular microenvironment in supporting the growth of human cancer cells freshly harvested from malignant ovarian ascites and to determine whether there are differences among subsets of ascites-derived cancer cells in terms of tumorigenic capacity in the conventional murine xenograft model and in the hESC-derived microenvironment.</p><p><b>Experimental Design:</b> Freshly harvested malignant ovarian ascites-derived cancer cells and six derivative ovarian cancer cell subpopulations (CCSP) were characterized for ovarian cancer–associated biomarker expression both <i>in vitro</i> and <i>in vivo</i> and for their capacity to generate tumors in the two models.</p><p><b>Results:</b> Ovarian cancer–associated biomarkers were detected in the ascites-derived cancer cells and in the six newly established CCSPs. Nevertheless, certain CCSPs that did not develop into tumors in a conventional murine xenograft model did generate tumors in the hESC-derived cellular microenvironment, indicating variable niche dependency for the tumorigenic capacity of the different CCSPs. The hESC-derived microenvironment provided an improved niche for supporting growth of certain tumor cell subpopulations.</p><p><b>Conclusions:</b> The results highlight the experimental utility of the hESC-derived cellular microenvironment to enable functional distinction of CCSPs, including the identification of cells that do not grow into a tumor in the conventional direct tumor xenograft platform, thereby rendering such cells accessible to characterization and testing of anticancer therapies.</p></div>