Genetic approach fluorescently marks cancer stem cells in-vivo

Researchers have developed a novel genetic approach to unravel how tumors grow in their natural environment, using a genetic tracing strategy to fluorescently mark individual tumor cells and follow their fate of their progeny over time.

Researchers at the Université libre de Bruxelles (Brussels, Belgium), in collaboration with the University of Cambridge (Cambridge, England), have demonstrated for the first time the existence of cancer stem cells during unperturbed solid tumor growth.

In a new study, the researchers developed a novel genetic approach to unravel how tumors grow in their natural environment. They used a genetic tracing strategy to fluorescently label individual tumor cells and follow their fate of their progeny over time.

The researchers found that in benign skin tumors, the majority of tumor cells have limited proliferative potential while only a minority have the capacity to persist long-term. This gives rise to progeny that occupy a big part of the tumor, consistent with the marking of long-lived cancer stem cells. "This was particularly exciting to visualize for the first time cancer stem cells in action in their natural environment," comments Gregory Driessens, Ph.D., first author of the study.

In collaboration with Prof. Benjamin D. Simons of the Cavendish Laboratory at the University of Cambridge, the researchers developed a mathematical model of their clonal analysis, which in benign tumors supports the existence of hierarchical organization of the tumor 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. "The stochastic mode of division in tumor cells mimics the situation found in normal tissue and suggests that tumor heterogeneity can be the consequence of this particular mode of division rather than be necessarily the result of a Darwinian selective process," explains Simons.

Altogether, the 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 tumor growth. “This new approach will be important to better define the mode of tumor growth in different types of cancer, metastasis, and tumor relapse after therapy, which may have important implications for the development of new therapeutic strategy,” explains Cédric Blanpain, MD, Ph.D., senior author of the study.

The work has been published in Nature; for more information, please visit http://www.nature.com/nature/journal/vaop/ncurrent/full/nature11344.html.

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