Understanding the migration mechanisms of metastatic cells to fight cancer

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When a tumor develops in an organism, it is very common for the cancer cells to leave the tumor and settle in another organ where they proliferate, creating what is called metastasis. This process is an important factor in mortality since it means the worsening of the disease. Hence the interest in better understanding what happens during this phenomenon. This is what the multidisciplinary team of Carine Michiels, researcher at the NARILIS Institute of UNamur, and Davide Bonifazi, researcher at the University of Vienna, did in the framework of the PACMAN research project funded by the FNRS. The results of this study are published in the journal Neoplasia.

To understand this, we need to imagine the cancer cells within a tumor. These cells, which are equipped with small extensions (which we will call feet), are grouped on fibers (the path). During the development of metastatic disease, cancer cells migrate out of the tumor, along these fibers, into blood vessels, from which they spread throughout the body. In simple terms, it is as if these cells are "walking" along the fibers. A protein found in these fibers, fibronectin, seems to facilitate this migration.

The research project focused on metastatic breast cancer cells. As shown in the illustration, a first experiment was performed in which a fragment of fibronectin was distributed in an increasing gradient on a gold surface. Cancer cells were then deposited on the surface and were found to move in the direction of the gradient (1). It is a bit like the arcade game PACMAN, the acronym of the project, in which PACMAN moves by swallowing pellets. However, if this experiment (2) is repeated while keeping the concentration of the fibronectin fragment constant, the cells do not move. The researchers then "removed" the feet of these cells (3) and found that the cells no longer migrated. These feet are therefore an essential component of metastatic cells. A "proteomic" study of the footless cells identified the foot recycling process as a process involved in the ability of cancer cells to migrate.

This study on the understanding of these fundamental mechanisms could therefore, in the long term, make it possible to detect metastases at an early stage of the disease or to study the means of preventing a tumor from releasing metastases and, thus, reduce the risks of complications and mortality related to this type of cancer.study the means to prevent a tumor from releasing metastases and, thus, reduce the risks of complications and mortality related to this type of cancer.

FNRS PACMAN RDP: Carine Michiels (UNamur) and Davide Bonifazi (University of Vienna)

A former UNamur PhD student, Sophie Ayama, who did her dissertation on the topic, was a finalist in My Thesis in 180 Seconds (MT180) in 2019. For those who are interested, here is the video of her presentation entitled "The New Adventures of PACMAN"

To see the full article: https://pubmed.ncbi.nlm.nih.gov/35763908/

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