In a study published in Nature, researchers lead by Cédric Blanpain, MD/PhD, WELBIO investigator at the IRIBHM, Université Libre de Bruxelles, Belgium, in collaboration with Pr. Benjamin Simons, University of Cambridge, UK, demonstrate for the first time the existence of cancer stem cells during unperturbed solid tumor growth.
Cancer stem cells have been described in different human cancers including skin cancers. Cancer stem cells have been hypothesized to sustain tumour growth, to resist to chemotherapy and radiotherapy and to be responsible for tumor relapse after therapy. Until now, cancer stem cells have been demonstrated by their ability to reform tumour upon transplantation into immunodeficient mice. These studies show the potential of cancer cells in these experimental conditions but do not necessarily reflect the actual fate of tumour cells in their native environment. The existence of cancer stem cells during unperturbed tumour growth remained unproven so far.
In this new study published in Nature, Gregory Drisessens and colleagues developed a novel genetic approach to unravel how tumours grow in their natural environment. They used a genetic tracing strategy to fluorescently mark individual tumour cells and follow their fate of their progeny overtime. Interestingly, they found that in benign skin tumours, the majority of tumor cells have limited proliferative potential, while only a minority have the capacity to persist long term, giving rise to progeny that occupy a big part of the tumour, consistent with the marking of long lived cancer stem cells.
In collaboration with Pr. Benjamin D. Simons, Cavendish Laboratory, University of Cambridge, UK, they developed a mathematical model of their clonal analysis, which in benign tumours supports the existence of hierarchical organization of the tumour with long lived stem cells and short lived committed progenitors. By contrast, in invasive cancer, the hierarchical organization changes with the emergence of cancer stem cell with limited potential for terminal differentiation.
Altogether, this study provides novel and important insights into the mode of tumor growth, and demonstrates for the first time the existence of cancer stem cells during unperturbed solid tumour growth.
Driessens et al, Defining the mode of tumour growth by clonal analysis. Nature 2012, DOI: 10.1038/nature11344