CD133+ cells contain cancer stem cell-like properties in Malignant Mixed Mullerian Tumor (Carcinosarcoma) of the Uterus

Cancer stem cells (CSCs) that display tumor-initiating properties have recently been identified. We herein identify and characterize CSCs in human uterine carcinosarcoma, a highly aggressive and therapy-resistant gynecologic malignancy, which is considered to be of mesodermal origin. FU-MMT-1, a cell-line, which was established by us (Emoto M, Cancer 1992) from a patient with uterine carcinosarcoma, was evaluated. FU-MMT-1 contained a high population of CD133, CD44, CD90, and CD29 positive cells. Using the magnetic bead cell separation method, we isolated CD133+ cells, which predominantly form spheres in culture. These CD133+ cells form transplantable tumors in vivo. A qRT-PCR analysis of the genes implicated in stem cell maintenance revealed that CD133+ cells express significantly higher levels of OCT4, NANOG, and BMI-1 than CD133－ cells. Moreover, CD133+ cells showed a high expression of PAX2 and WNT4, which are the essential genes in Mullerian duct formation. The tumor derived from CD133+ cells replicated vimentin, ERα, ERβ, and PR expressions　of the parent tumor. These findings suggest that CD133+ FU-MMT-1 cells have the characteristics of CSCs and Mullerian mesenchymal progenitors. CD133+ and CD133- population of FU-MMT-1 cells were analyzed by microarray.