Midbody Accumulation in Breast Cancer Stem Cells

Abstract : Breast cancer is a complex disease that develops from epithelial lesions confined to breast ducts and lobules and progresses rapidly to become locally invasive and finally metastatic. Our recent studies show that breast cancer cells undergo asymmetric events during cell division that generate different daughter cells. One daughter receives the singular midbody (MB) that is made during every cell division. The cell with this so-called postmitotic midbody derivative accumulates additional MBds with successive divisions. In breast tumor sections, rare cells stain for MBds adjacent to the basal layer, the position of putative breast cancer stem cells. MBds are present in high numbers in several human breast cancer cell lines and in human tumors, but are rarely found in normal breast epithelial cell lines or breast tissue. MBds are also found in several well-characterized mouse and human stem cell niches but not in adjacent transit amplifying or differentiating cells. These results suggest that MBds are in almost exclusively in stem cells and putative breast cancer stem cells (CSS). This idea is consistent with the emerging view that breast cancer develops from transformation of stem cells. Based on these observations, we propose that MBds 1) will serve as markers for breast CSCs, 2) may have diagnostic/prognositc value for breast cancer progression and 3) could directly contribute to breast carcinoma. To test this, we propose the following aims: 1) Quantify MBds in breast tumors and cell lines and compare with normal breast epithelial cells. 2) Test MBd-containing breast cancer cells for CSC activities in vivo and in vitro. 3) Test MBds for their ability to confer breast cancer stem cell properties by disrupting MBd inheritance or RNAi.