To search for these potentially dangerous cells, Kondo's team tested several cancer cell lines for the presence of side populations (SP) of cells containing the breast cancer–resistant protein 1 (BCRP1), an ATP-dependent transporter found in many stem cells. Of six lines tested, four had BCRP1-containing SP cells that accounted for between 0.4% and 2.1% of the total population.
The growth of SP cells requires basic fibroblast growth factor (bFGF) and platelet-derived growth factor (PDGF). “bFGF seems to be essential for the self-renewal of C6 stem cell but is not enough to induce stem cell proliferation” says Kondo. In the presence of both growth factors, the SP cells proliferate but maintain their stem cell–like qualities.
When the authors isolated SP cells and allowed them to repopulate a culture, they found that the cells produce both SP and non-SP cells. By contrast, non-SP cells cannot be induced to take on SP traits, suggesting that the SP cells are the population's stem cells.
It is these SP cells that seem to be responsible for malignancy. SP cells injected into immunologically compromised mice generate aggressive, invasive cancers, whereas non-SP cells generally give rise only to local tumors. Since both cell types contain the same oncogenic mutations, the difference is probably due to epigenetic differences such as silencing, says Kondo. He and others are already looking for possible stem cell behavior switches, such as Bmi-1, an epigenetic factor recently shown to be concentrated in stem cells. ▪