Niche-dependent tumorigenic capacity of malignant ovarian ascites-derived cancer cell subpopulations.
OBJECTIVE
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.


METHODS
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 in vitro and in vivo and for their capacity to generate tumors in the two models.


RESULTS
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.


CONCLUSIONS
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.
Katz
Ehood
E
Rappaport Faculty of Medicine and Research Institute, Technion-Israel Institute of Technology, Haifa, Israel.
Skorecki
Karl
K
Tzukerman
Maty
M
D018262:Adenocarcinoma, Clear Cell / Q000473:pathology*; D000818:Animals; D001201:Ascites / Q000473:pathology*; D014408:Biomarkers, Tumor / Q000032:analysis; D004195:Disease Models, Animal; D005260:Female; D006801:Humans; D051379:Mice; D016513:Mice, SCID; D008875:Middle Aged; D009368:Neoplasm Transplantation; D010051:Ovarian Neoplasms / Q000473:pathology*; D014183:Transplantation, Heterologous
D014408:Biomarkers, Tumor