Stem Cells Not Progenitors Can Trigger Skin Cancer Growth

Cancer researchers have discovered that stem cells can initiate development of malignant skin tumors, while progenitor cells are limited to triggering only benign growths.

A progenitor cell is similar to a stem cell, in that it has a tendency to differentiate into a specific type of cell, but is already more specific than a stem cell and is pushed to differentiate into its "target" cell. The most important difference between stem cells and progenitor cells is that stem cells can replicate indefinitely, whereas progenitor cells can divide only a limited number of times.

Investigators at the Université Libre de Bruxelles (Belgium) and the University of Cambridge (United Kingdom) sought to identify the type of cells that initiated formation of basal cell carcinoma, the most common form of skin cancer. To this end they assessed the impact of oncogenic hedgehog signaling in distinct cell populations and their capacity to induce cancer growth.

They reported in the July 8, 2016, online edition of the journal Nature that in a transgenic mouse model system only stem cells, and not progenitors, were competent to initiate tumor formation upon oncogenic hedgehog signaling. Clones derived from stem cells were able to overcome apoptosis and continue to divide and proliferate unchecked, developing into basal cell carcinoma. In contrast, the growth of clones derived from progenitor cells was checked by increasing levels of apoptosis, leading to the formation of benign lesions.

"It is incredibly rare to identify a cancer cell of origin and until now no one has been able to track what happens on an individual level to these cells as they mutate and proliferate," said senior author Dr. Cédric Blanpain, a professor at the Université Libre de Bruxelles. "We now know that stem cells are the culprits: when an oncogene in a stem cell becomes active, it triggers a chain reaction of cell division and proliferation that overcomes the cell's safety mechanisms."

"While this has solved a long-standing scientific argument about which cell types can lead to invasive skin tumors, it is far more than just a piece of esoteric knowledge," said contributing author Dr. Benjamin Simons, professor of physics at the University of Cambridge. "It suggests to us that targeting the pathways used in regulating cell fate decisions - how stem cells choose between cell proliferation and differentiation - could be a more effective way of halting tumors in their tracks and lead to potential new therapies."

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Université Libre de Bruxelles
University of Cambridge