11 Jul Stem Cells, Not Their Progeny, Found Competent To Initiate Basal Cell Skin Cancer Formation

MedicalResearch.com Interview with:

Dr. Cédric Blanpain

Cédric Blanpain, MD, PhD
Professor of Stem Cell and Developmental Biology
WELBIO, Interdisciplinary Research Institute (IRIBHM)
Université Libre de Bruxelles (ULB)
Belgium
MedicalResearch.com: What is the background for this study?

Response: Many cancers arise from tissues maintained by stem and progenitor cells that ultimately give rise to non-dividing terminally differentiated cells. However, little is known about the contribution of stem cells and progenitors to cancer initiation. During tumor initiation, cells targeted by oncogenic mutations undergo a series of molecular changes leading to their clonal expansion and the acquisition of invasive properties. How exactly oncogenic mutations impact on the rate of stem cell and progenitor division, and change the proportion of divisions that result in symmetric and asymmetric cell fate, allowing clonal expansion and tumor progression is poorly understood. In this new study, we define for the first time the clonal dynamics that lead to skin cancer initiation using the basal cell carcinoma, the most frequent tumor in humans, as a model.

MedicalResearch.com: What are the main findings?

Response: In this study, we used a genetic tracing strategy that allowed us to mark the stem cells and progenitors that express the oncogene and follow the fate of their progeny over time. Interestingly, we found that only stem cells and not their progenitor cell progeny were competent to initiate tumor formation upon oncogenic activation. Specifically, we observed that oncogenic activation in progenitors lead to the generation of lesions that are frozen into pre-tumorigenic state and cannot progress into invasive tumours.

In contrast, oncogene expression in stem cells resulted in a more rapid clonal expansion characterized by an increase in self-renewing divisions combined with a higher resistance to cell death, and leading in turn to the development of clones that progress into invasive tumours. These data demonstrate that targeting stem cells, which reside at the top of the cellular hierarchy in the skin epidermis, was necessary for tumor formation.

MedicalResearch.com: What should readers take away from your report?

Response: This study provides important insights into the changes in the cellular dynamics that lead to tumor formation and demonstrates that the capacity of oncogene expressing cells to induce tumor formation depends on the specific clonal dynamics of the cancer cell of origin. These new findings not only demonstrates that the cancer cell of origin matters, but also that stem cells are particularly sensitive to tumor initiation due to their natural ability to self-renew and their resistance to oncogene mediated cell death.

MedicalResearch.com: What recommendations do you have for future research as a result of this study?

Response: The mode of tumour development described in our study suggests that therapy promoting differentiation or apoptosis should be effective in the treatment of basal cell carcinomas, and should lead to tumour regression and prevent tumour relapse. For this reason, I consider that we should focus on the development of strategies aimed at eliminating pre-cancerous legions or at impeding malignancy transformation.

MedicalResearch.com: Is there anything else you would like to add?

Response: This work was done in collaboration with Pr.Benjamin D Simons, Cavendish Laboratory and the Gurdon Institute, University of Cambridge, UK.

MedicalResearch.com: Thank you for your contribution to the MedicalResearch.com community.

Citation:

Adriana Sánchez-Danés, Edouard Hannezo, Jean-Christophe Larsimont, Mélanie Liagre, Khalil Kass Youssef, Benjamin D Simons and Cédric Blanpain.
Defining the clonal dynamics leading to mouse skin tumour initiation
Nature, 2016. DOI 10.1038/nature19069

Note: Content is Not intended as medical advice. Please consult your health care provider regarding your specific medical condition and questions.

More Medical Research Interviews on MedicalResearch.com

[wysija_form id=”5″]

Last Updated on July 11, 2016 by Marie Benz MD FAAD