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Scientists identify 'cell of origin' in skin cancer

Understanding the first cells to start the development of cancer may help in the development of more effective treatments, researchers said.

By
Stephen Feller
The green-labelled cells show a basal cell carcinoma in mouse tail epidermis derived from a single mutant stem cell and expanding out of the normal epidermis stained in red, which researchers say is rare finding of a cancer's cell of origin. Photo by Adriana Sánchez-Danés/University of Cambridge
The green-labelled cells show a basal cell carcinoma in mouse tail epidermis derived from a single mutant stem cell and expanding out of the normal epidermis stained in red, which researchers say is rare finding of a cancer's "cell of origin." Photo by Adriana Sánchez-Danés/University of Cambridge

CAMBRIDGE, England, July 8 (UPI) -- Researchers have found the "cell of origin," or first cell to give rise to cancer, in the most common form of skin cancer, which may help in designing future treatments for the disease.

While many cells can give rise to non-cancerous lesions, researchers at the University of Cambridge found only stem cells can develop in invasive tumors, suggesting that identifying targets in cells responsible for differentiation and growth could lead to better cancer treatments.

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Skin stays healthy by replacing dying skin cells with new cells, a process maintained by progenitor cells, which come from stem cells, that divide and become fully functional skin cells. These cells are supported by stem cells to replace cells in the future when they die.

Damaged DNA or activation of oncogenes can trigger the growth of invasive cells and development into tumors. Researchers have been unsure, however, what type of cell is responsible -- stem cell, progenitor cell or both.

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"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," Ben Simons, a professor at the University of Cambridge, said in a press release. "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."

For the study, published in the journal Nature, researchers used mice whose genes were altered to activate an oncogene in stem and progenitor cells, pairing the oncogene with a fluorescent marker so the oncogene could be spotted and tracked in daughter cells as they split and become skin cells.

The researchers were able to see that oncogenes activated in mutated stem cells survived apoptosis, a system of programmed cell death for when something has gone wrong, instead continuing to divide and grow, becoming basal cell carcinoma. Progenitor cells, on the other hand, experience increasing levels of cell death, forming benign, non-cancerous lesions.

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"It's 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 Cédric Blanpain, a professor at the Université libre de Bruxelles in Belgium. "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."

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