It is estimated that 55,000 Canadians have brain cancer and that approximately 10,000 new cases are diagnosed every year. Although improved anti-cancer therapies have made it possible to extend the lives of many people, molecular targeting and current research models remain inadequate.
Several recent studies have shown that, far from forming a homogeneous mass of rapidly proliferating cells, tumour cells are heterogeneous in how they proliferate and differentiate. One subpopulation of these cells possesses certain characteristics of normal stem cells, such as the capacity to regenerate and to differentiate into tumour cells. These cancer stem cells (CSCs) are often relatively quiescent and are therefore not really affected by therapies that target rapidly dividing cells. In addition, the overexpression of transporters that excrete anti-tumour agents from cells contributes to resistance to the conventional chemotherapy and radiation treatments used to kill cancer cells. It is therefore of vital importance to develop and validate models that make it possible to fully understand the role of CSCs in tumour development.
Recently, CD133 or Prominin-1, a transmembrane glycoprotein, was identified as a CSC marker. As a result of this observation, researchers are now endeavouring to characterize CD133(+) CSCs. With this goal in mind, two experimental brain tumour cell implantation strategies are currently under study: one subcutaneous and the other intracranial. Remarkably, CD133(+) CSCs are expressed only in the original cerebral environment in which the tumour developed [1]. Moreover, isolating CSCs from solid brain tumour samples using MACS, a separator comprised of magnetic beads coupled with an anti-CD133 antibody, will make it possible to identify the molecules involved in the phenotype infiltrating brain tumours in order to target them more effectively.
It is now known that the growth of several types of cancer is due not only to the cancer cells themselves, but also to the involvement of CSCs, which are also responsible for tumour relapse. With the identification of CSCs, we can now devise ways to test and validate new anti-cancer therapies in much more adequate models in order to understand the role of CD133(+) CSCs. Future discoveries will pave the way for specific targeting of CSCs, which will make it possible to identify therapeutic molecules more effectively in both clinical testing and fundamental research and to develop new treatment strategies for brain tumours.
[1] Annabi B, Rojas-Sutterlin S, Laflamme C, Lachambre MP, Rolland Y, Sartelet H, Béliveau R. (2008) Tumor environment dictates medulloblastoma cancer stem cell expression and invasive phenotype. Mol Cancer Res. 6, 907-916.
