Tumor Initiating Cells in Mesenchymal Neoplasms

Despite the clonal origins of tumors, the majority of neoplasms are composed of a heterogeneous population of cells. The origins of this phenotype these cells have the potential to get can be associated with cancer stem cells or tumor initiating cells have the potential to self-renew and to differentiate giving rise to all cell types compromising a heterogeneous malignancy. These cells are clinically important as they preferentially give rise to tumors and are therefore hypothesized to account for the longevity and recurrence of neoplastic lesions. Cancer stem cells have been identified from a broad range of hematopoietic, neural and epithelia tumors; however, their function in mesenchymal neoplasms is less well defined. Using the side population assay, we identified a subpopulation of cells within mesenchymal neoplasms, referred to as side population cells, which are enhanced for tumor initiating potential. Importantly, we show a correlation between the percentage of side population cells and tumor grade suggesting clinical prognostic value as the proportion of side population cells may be a predictor of patient outcome. Interestingly side population cells show distinct molecular features when compared to non-side population cells and manipulation of these molecular mechanisms reduces the ability of side population cells to initiate tumor formation in osteosarcoma cell lines. In conjunction with these experiments, we also sought to determine the cellular origins of the mesenchymal neoplasm, aggressive fibromatosis. Using mouse models we show the influence of a mesenchymal precursor cells in the development of this malignancy. These results identify important biological features of mesenchymal neoplasms from which the development of targeted treatment strategies can begin.Ph