Jacky Goetz: Cancer and Metastasis, in Search of the Forces at Work

The aggressiveness of a tumor brings into play various biomechanical forces of its own cells and those of its close environment. These are phenomena that Jacky Goetz, head of the Tumor Biomechanics team in Strasbourg, observes and then deciphers. His research has earned him two awards and a certification.

One reason why cancers are so dangerous is their ability to produce metastases: cells that pass through the bloodstream to form a new tumor. « My team and I are studying the mechanisms that enable circulating breast cancer cells to leave the bloodstream and colonize a new tissue, » explains Jacky Goetz, Inserm research director at Strasbourg University’s Molecular Immunology and Rheumatology Laboratory*. His original approach, based on the study of the biomechanical forces involved in these phenomena, has enabled him to start unravelling this mystery. An approach that in 2020 earned him the French Academy of Sciences Simone and Cino Del Duca Foundation Grand Prize in Oncology, the Ruban rose Avenir grant for an innovative breast cancer research program and, this year, French League against Cancer certification.

While Goetz’ current focus is on the last stage of cancer progression, his initial interest was piqued by the broader question of how a tumor is able to send cells to invade other organs. And just like this phenomenon, his career has been marked by key stages that have led him to his present-day research. « It was in eleventh grade that I first developed an interest in science. I discovered that you could visualize proteins in 3D from all angles, which appealed to my artistic side, » says the researcher. This interest then intensified at the end of my master’s degree in biology. To find out whether academic research really was for me, I did a one-year voluntary internship with Inna Gerasymova, PhD student at the pharmacy faculty in Strasbourg who was working on the migration of astrocytomas, a cancer of the brain. » And that sealed the deal for what was to become a lifelong interest in cancer progression research.

Having completed his post-graduate diploma (DEA), and as a nod to the cancer cells that travel within the body, he decided that he would leave his home port « because my partner and I wanted to see new horizons. » So in October 2003, he set off to do his dissertation in Canada, under the supervision of Robert Nabi at the University of British Columbia. « I studied the ability of tumor cells to anchor themselves to the surrounding microenvironment under the influence of its biomechanical forces, » he explains. In addition, Nabi, whose scientific curiosity is immense, has played a major role in constructing my personality as a researcher. » While Canadian life with the omnipresence of nature was ideal for the scientist, who is also a triathlete, the couple decided to move closer to Strasbourg for family reasons. In January 2008, he did his postdoctoral fellowship in Spain, in Miguel Angel del Pozo’s team at the Carlos III National Center for Cardiovascular Research in Madrid. « There I studied how certain originally healthy cells are able to remodel the tumor environment, » explains Goetz. In parallel, his interest in microscopy led him to develop approaches to visualizing the key stages of metastatic progression in animal models.

Seeing is believing

At the beginning of 2010, with the desire to live in a less built-up environment, the sportsman headed for Strasbourg and Julien Vermot’s laboratory at the Institute of Genetics and Molecular and Cellular Biology** in Illkirch. During this second post-doctoral fellowship, he learned to master the zebrafish model and studied, thanks to « intravital » microscopy on living embryos, the capacity of the blood vessel wall to respond to flow forces. « This research is very useful for our current studies on the formation of metastases, » he emphasizes. In fact, since 2013 and the creation of his Inserm group, he has been implementing this Seeing is believing approach in order to study the progression of breast cancer, which has resulted in four major studies. The team shows that the blood vessel wall remodels itself around the circulating tumor cell, impeding its circulation. This allows it to exit the bloodstream and form a metastatic focus. During the same process, the team observes that cancer cells possess an adhesion mechanism enabling them to attach to the vessel wall and resist flow forces. In addition, the team is looking at extracellular vesicles. « These lipid droplets of about 100 nanometers carry many active molecules. Secreted by tumors before the cancer cells’ departure, they colonize the organs and prepare the ground for them to become metastatic, explains Goetz. Now, using intravital microscopy, we have been able to visualize them for the first time worldwide. » The team then showed that if tumor cells lack the RAL‑A and RAL‑B genes (RAS Like Proto-Oncogene A and B), the vesicles they secrete become less effective. « Breast tumors that weakly express these two genes are less aggressive, adds the researcher. The molecular analysis of these vesicles collected by a simple blood test could therefore improve the diagnosis of this cancer. » Fundamental research that brings hope, as evidenced by the many awards he has received.

Notes :
* unit 1109 Inserm/Strasbourg University, Tumor Biomechanics team
* unit 1258 Inserm/CNRS/Strasbourg University; Imperial College London (UK)