Tumor stroma and differentiated cancer cells can be originated directly from polyploid giant cancer cells induced by paclitaxel

Paclitaxel is widely used to treat cancer patients through the blocking of mitosis and result in formation of polyploidy giant cancer cells (PGCCs), which are generally believed to be nondividing cells or in mitotic catastrophe. Here, we showed that PGCCs following the treatment of paclitaxel of MCF-7 breast cancer cell line have capability to generate regular-sized progeny cells through budding. The PGCCs not only grew into well-differentiated cancer cells that formed cancer organotypic structures in vitro but also trans-differentiated into multiple tumor stromal cells including myoepithelial, endothelial and erythroid cells. PGCCs formed glandular and vessel-like cancer organotypic structures that expressed normal stem cell markers. These progeny cells generated from PGCCs showed decreased ability of proliferation, invasion and tumor growth and became more resistant to paclitaxel than parental MCF-7 cells. These results demonstrated that paclitaxel-induced PGCCs have properties of cancer stem cells that can generate both epithelial cancer cells and multilineage of stromal cells. PGCCs are not only the morphogenic determinant to tumor histogenesis and but also contribute to paclitaxel resistance. What's new? Paclitaxel is a mitotic inhibitor and is widely used to treat cancer patients by inhibiting cell mitosis and inducing the formation of polyploidy giant cancer cells (PGCCs). Here the authors show that PGCCs derived from the MCF-7 breast cancer cell line have properties of stem cells. They can differentiate into multiple lineages of tumor stromal and differentiated cells and form glandular and vessel-like cancer organotypic structures in vitro. The authors see their findings as evidence that tumor-associated stromal cells, often considered non cancer-derived, can be directly generated from cancer cells. In addition, they conclude that PGCCs through their properties as cancer stem cells may contribute to paclitaxel resistance and tumor progression.