Low Oxygen Tension for Cancer Stem Cells: Keeping it Real

Tampa, FL -

We have previously discussed the importance of mimicking the physiological environment when studying different types of stem cells, so why would this not be true also for tumor stem cells?  Specifically, it is known that hematopoietic stem cells reside in the hypoxic niche of the bone marrow.  This can also be said of neural progenitors.  Both of these types of cells, when grown under hypoxic conditions ex vivo has been shown to grow better.  For example, some people even use "hypoxic preconditioning" in order to make mesenchymal stem cells work better. 

It is known that tumor stem cells are a "sick caricature" of the normal stem cell.  This is supported by the fact that tumor stem cells, share with normal stem cells, things like Fas induced death resistance, multiple drug resistance, immune evasion genes, and preference for the G0 stage of cell cycle.  Therefore, would it not make sense for tumor stem cells to also share with healthy stem cells a preference for hypoxic tissue?

A recent paper (McCord et al. Physiologic Oxygen Concentration Enhances the Stem-Like Properties of CD133+ Human Glioblastoma Cells In vitro. Mol Cancer Res. 2009 Apr;7(4):489-97) demonstrated that glioma stem cells purified from the CD133 fraction had increased replicative potential when cultured at 7% oxygen, which resembles in vivo hypoxic conditions, as opposed to 20% oxygen, which is what everyone usually uses in tissue culture. 

At 7%, the cells had enhanced ability to diferentiate into glia and neural cells, and were expressing stem cell markers higher than cells grown at 20%.

Microarray analysis was also performed, which revealed changes in 140 genes.

This is the first study to our knowledge comparing tumor stem cells at hypoxic and normoxic conditions.  It will be important to see what difference this has on functionally relevant parameters such as expression of immune evasion/antiapoptotic/metastasis genes.