Because we now know that the ectopic implantation of a population of cells requires complex interactions between the regurgitated cells and the host tissue, which must be able to offer the new arrivals the chance to survive and grow ⁽¹⁾. In other words, the endometrial cells have to be able to invade other tissues, escape the watchful eye of the immune system, induce the development of new blood vessels (angiogenesis) and lymph vessels in their new location of choice, and finally, proliferate locally. Michelle Nisolle’s work has explored these various aspects.

First step of an invasion: throw down the anchor on unknown territory. It is thanks to the development of experimental human endometrial transplantation models in mice that Michelle Nisolle was able to analyse the interactions that are formed between the endometrial cells and the host tissue, with a view to creating a micro-environment favourable to their implantation. These interactions bring the glycoproteins fibronectin and laminin into play. Acting as an adhesive, they exercise their action through receptors from the family of integrins, well known for their key role in the cancerous metastasis cascade (read the article “Preparing for the crime”).

Another similarity: in order to be able to penetrate deep into the host tissue, the endometrial cells must first detach themselves from their neighbours with whom they are attached by cellular adhesion proteins from the cadherin-E family (see article “SIBLINGs, cancer’s multifunctional weapons”). We know that the less cancerous cells express cadherin-E, the more they are potentially invasive. And yet, it seems that the cells from the uterine mucous membrane of women affected by endometriosis express less of this protective protein than the endometrial cells of women who don’t suffer from this condition. Which is probably why the former have a higher invasive potential.

The formation of new blood cells is another essential step in successful ectopic implantation in contrast to the normal uterine mucous membrane cells; they create a new mucous membrane every month, which receives the nutrients it needs for its short 28-day life through the newly formed blood vessels. There was only one step from here to thinking that the endometrial cells were capable of inciting the generation of new blood vessels somewhere other than in their usual environment. Research published in 2009 ⁽²⁾ confirmed this, also thanks to the transplantation model in mice, “we showed that this neovascularisation was due to a connection between the mouse’s vessels and those of the grafted endometrium. These chimerical vessels of human and mouse cells can already be observed after a few days, allowing the graft to survive”.

(1) Pathogenèse de l’endométriose, Nisolle M, Alvarez ML, Colombo M et Foidart JM, in Gynécologie Obstétrique & Fertilité 35 (2007) 898–903.

(2) doi10.1093/humrep/dep203