Abstract
Abstract The cancer stem cell (CSC) hypothesis stipulates that tumors follow a hierarchical organization where a subpopulation of cells endowed with stem cell characteristics initiates and maintains the malignant progression. Using the murine MCA sarcoma model system, a widely recognized model for studying cancer immunosurveillance and rejection mechanisms, we sought to explore how hierarchical tumor progression occurs during cancer immunosurveillance. The first step was to define CSC in the MCA sarcoma model. We identified an interesting heterogeneity of the tumor population based on Sca1 and CD90 expression. Purification of the Sca1+ and Sca1+/CD90+ in various cell lines and subsequent in vitro culture demonstrated that the Sca1+/CD90-population is able to regenerate the initial tumor heterogeneity. Transplantation of those two populations in RAGxγc-/- hosts demonstrated either a more rapid onset of sarcoma in mice injected with Sca1+ cells. Interestingly, phenotypic analysis of escaping tumors revealed an increase in Sca1+ cells. Finally, in vitro treatment with IFNg led to a substantial increase in Sca1 expression that correlated with an increase in cells' stemness properties as suggested by the elevated sphere forming capacity of IFNg treated cells. This data suggest that cancer stemness may be modulated by anti-cancer immune responses and may represent an additional mechanism of tumor immune escape.
Published Version
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