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A closer link between development and cancer

Vincent Favaudon, radiobiologiste, chercheur à l'Institut Curie (U612 INSERM) et directeur de recherche émérite INSERM.

Les recherches de Vincent Favaudon et de son équipe sont consacrées aux bases de la radiothérapie et de la chimiothérapie antitumorale. Elles comprennent l'étude du mode d'action des drogues antitumorales, des effets de ces drogues en association avec les radiations ionisantes, et de la dynamique de la réponse cellulaire (signalisation, réparation) aux radiations.

Méthodologies expérimentales :
Biologie des radiations, Radiobiologie, Pharmacologie moléculaire, Biologie cellulaire, Biologie moléculaire, Radiations ionisantes.

Ici : Accélérateur linéaire d'électrons de 4.5 MeV (CGR-MeV), pour des expériences de radiolyse pulsée à très haut débit de dose.

Working in close scientific collaboration, French and American researchers show that mechanisms at the origin of life also resemble mechanisms used by cancer cells to jeopardize life.

 

From the very first days on the pregnancy, the survival of the embryo depends on the placental cells that surround it and allow its implantation into the uterus. To allow this implantation, placental cells must develop specific capabilities: they migrate and invade tissues of the mother, while escaping her immune system, as it could reject and destroy the embryo. A research team at Institut Curie, working in France with teams at the French National Institute of Health and Medical Research (INSERM), the French National Center for Scientific Research (CNRS), Université Paris Descartes and Université Pierre et Marie Curie, as well as in the United States with a team at Massachusetts General Hospital and Harvard Medical School, studied placental cells to gain insight in the mechanisms underlying their astonishing capabilities. Among the 23,000 genes contained in each of our cells, these mechanisms – namely “epigenetic mechanisms” – select particular genes, which expression allow placental cells to support life.  No life without harmonious operations within placental cells.

Intriguingly, these French and American researchers have shown that several mechanisms used by placental cells to play their role foreshadow mechanisms that could later be leveraged by cancer cells for migrating, invading organs and escaping immunity, thereby jeopardizing patients’ life.

This work that has just been featured in the scientific journal Epigenetics had been mainly conducted by a young scientist of Institut Curie, Dr. Akpéli Nordor, who has been commuting for the past three years between the Parisian labs of Dr. Thierry Fournier, a placenta expert, Pr. David Klatzmann, an immunology expert, and Pr. Dominique Bellet, a cancer expert, and the Bostonian lab of Dr. Martin Aryee, an expert big data analysis applied to epigenomics and genomics.

This pilot study opens exciting perspectives as it shows that research on placental cells can lead to new insights regarding cancer. In a clinical setting, studies performed on the placenta had already led to major discovery in oncology: one of the more striking example is the initial description in the placenta of programmed death-ligand 1 (PD-L1), a molecule targeted by immunotherapies that are currently revolutionizing the management of various cancers (1,2). In philosophical terms, the similarity between mechanisms used by placental cells, that support the very first steps of life, and cancer cells, that can jeopardize it, offers us an occasion for reflection on the value of human life and on its inherent fragility.

Noteworthy, the research program that led to the surprising results today has been funded since its inception not only by public institutions but also by private donors committed in supporting high risk research programs. This highlights once again the pivotal role of philanthropy in supporting audacious scientific programs (3-5).

 

 

References:

(1) Couzin-Frankel J. « Breakthrough of the year 2013. Cancer immunotherapy. » Science, 2013.

(2) H. Dong et al. « B7-H1, a third member of the B7 family, co-stimulates T-cell proliferation and interleukin-10 secretion. » Nature Medicine, 1999.

(3) C. Leaf « Why We’re Losing the War on Cancer—and How to Win It. » Fortune, 9 mars 2004.

(4) G. Colata. « Grant System Leads Cancer Researchers to Play It Safe. » The New York Times, 28 juin 2009.

(5) A. Maxmen. « Taking risk to transform science. » Cell, 2009.

 

 

The early pregnancy placenta foreshadows DNA methylation alterations of solid tumors.

Nordor AV, Nehar-Belaid D, Richon S, Klatzmann D, Bellet D, Dangles-Marie V, Fournier T, Aryee MJ

Epigenetics. 2017 Jul 5:0. doi: 10.1080/15592294.2017.1342912.