Scientists have long wondered which cells give rise to tumors at the start of cancer development. In research just published in the journal Nature, a team of researchers has identified which cells have the potential to grow into tumors.
Cancer can arise in a few different ways, including from damaged DNA. Many cancers are triggered by the activation of genes known as “oncogenes”. Oncogenes cause reactions that may ultimately lead to cancer development, prompting some people to get tested for their presence if cancer runs in their family. The researchers focused on these types of cancer, using mice that were genetically modified to have activated oncogenes.
The research team, led by scientists from the University of Cambridge and the Université Libre de Bruxelles, studied a group of mice with active oncogenes. Specifically, the mice were modified so that the genes were switched on in both stem cells and progenitor cells. The researchers then analyzed the cells with a combination of fluorescent imaging and mathematical models. They found that progenitor cells can develop into harmless lesions but only the stem cells were capable of giving rise to tumors. The cancerous stem cells were able to bypass a process called apoptosis, also known as programmed cell death. This mechanism is normally used to kill off damaged cells before they can proliferate and cause further damage. The affected stem cells were able to avoid this fate, continuing to grow and reproduce unchecked. The progenitor cells, however, were affected by apoptosis and gave rise to benign lesions.
Researchers have now identified stem cells as being the cancer cells of origin. If these cells become cancerous, possibly triggered by oncogenes, they skip apoptosis processes and continue to proliferate. This leads to the formation of malignant tumors. On the other hand, affected progenitor cells are susceptible to apoptosis mechanisms, resulting in benign lesions. These new findings further cancer research efforts, allowing us to develop better treatments in the future.
Sánchez-Danés, A et al. Defining the clonal dynamics leading to mouse skin tumour initiation. Nature (2016).