Low proteasome activity as a means to track and target breast cancer stem cells in-vivo.

摘要: Abstract #5055 Based on clinical observations, the existence of cancer stem cells (CSCs)/cancer initiating (CICs) in solid cancers has been postulated by radiation biologists and oncologists for decades. According to cell hypothesis, only a small number CSCs/CISs within tumor have ability repopulate an entire while their progeny does not. tumors can now be identified prospectively gliomas, head & neck cancers, pancreatic colon prostate melanomas, breast cancers. are thought mostly quiescent relatively resistant conventional anti-cancer therapy.
 Breast CSCs/CICs enriched populations with high CD44 low or absent CD24 expression. Unfortunately, detection CSCs/CISs, using expression analysis, requires dissociation antibody staining surface markers. We recently discovered that cells, specially CSCs/CICs, proteasome activity. In order utilize this novel marker identification we developed retroviral vectors coding fusion proteins between thymidine kinase (TK), fluorescent protein ZsGreen c-terminal degron murine ornithine decarboxylase (cODC). stably transfected human lines (MCF-7, MDA-MB-231, T47-D) reporter gene construct 26S activity.
 Our allowed us track responses therapy vivo via imaging, but also target them selectively suicide (TK) therapy. Thus, use our constructs allows specific elimination population ganciclovir preventing self-renewal in-vitro causing T47-D MDA-MB-231 xenograft regression vivo. Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 5055.