Resistance to Fas Induced Apoptosis in Glioma Stem Cells

Cedex, France -

The cancer stem cell appears to exist as a small fraction of the tumor mass that it relatively quiescent and resistant to killing by numerous types of chemotherapies because it has a set of drug efflux pumps.  One characteristic of cancer stem cells in tissues such as colon, lung, and brain is the expression of CD133, which is a stem cell marker found on respective non-malignant tissue stem cells as well.  Another property of tumor stem cells is that they seem to evade the immune system through expression of molecules such as CD55.

In a recent paper (Bertrand et al. Cancer stem cells from human glioma cell line are resistant to Fas-induced apoptosis. Int J Oncol 2009 Mar;34(3):717-27.) scientists have examined the efficacy of apoptosis induction in cancer stem cells generated from a glioma cell line.  It was found that by separating the cell line U87-MG into cells with "large" vs "small" characteristics, one could obtain CD133 positive stem cell-like cells in the cell population that was small by size !  This relation between small physical size and "stemness" was observed in the case of bone marrow derived stem cells called  Very Small Embryonic Like Cells (VSEL), as well as by Darwin Prockup's patent # 7,056,738 that covers selection of bone marrow stem cells with higher self renewing capacity based on small size.

The investigators noticed that while the glioma cells were in general sensitive to Fas-induced apoptosis, the small-sized glioma stem cell-like cells were not.  This was explained by the authors has having to do with the fact that the stem cell-like cells only had expression of monomeric Fas, which can not properly induce a death signal.  In contrast the large-sized glioma cells had oligomeric Fas expression which is believed to signal appropriately.