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How pressure limits tumors

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Scientific news INP CNRS
A team of researchers has demonstrated how the application of mechanical pressure on tumor cells limits their growth.
In the past, doctors had noticed that a slight mechanical compression sometimes limited the growth of tumors. Centuries later, a similar effect was observed in vitro : aggregates of tumor cells grow less quickly when subjected to a low pressure (a few kPa). Why ?

A team of researchers from the Laboratoire Interdisciplinaire de Physique (LiPhy, CNRS/Univ. Grenoble Alpes) in Grenoble, in collaboration with the Institut Lumière Matter (ILM, CNRS/Univ. Claude Bernard) in Villeurbanne and the Collège de France, hypothesizes that biological tissues are sensitive to low pressure due to their composite nature. They are in fact made up of cells surrounded by a hydrogel, the extracellular matrix. The latter, permeable to water and very compressible, is a thousand times more crushed and dehydrated than the cells under a pressure of a few kPa. By deforming, the extracellular matrix acts as a pressure sensor and inhibits proliferation. This work was published in the journal eLife.
To test the hypothesis, the authors proposed a new experimental strategy. The idea is to exert a selective osmotic pressure on cells or on the extracellular matrix, using osmolytes (biological molecules) of different sizes. Small osmolytes (< 5 nm, in blue in the figure) infiltrate the extracellular matrix without changing its compression state, but apply pressure on the cells. Large osmolytes (> 15 nm, green), on the other hand, cannot penetrate the extracellular matrix and compress the aggregate as a whole. The result is that for the same value of pressure (5 kPa), global compression of the aggregate inhibits its growth much more than compression selectively applied to cells. These results suggest that the deformation of the extracellular matrix effectively regulates the expansion of a tumor and also participates in the regulation of a healthy tissue.
The understanding of this mechanism would thus allow us to understand one of the mechanisms of self-regulation of the size of biological tissues (homeostasis) and, eventually, to restore this mechanism by pharmacological means when it is inhibited, which is the case in tumors.

Figure : The use of osmolytes of different sizes allows to select the site where the pressure is exerted, cells or extracellular matrix, and thus observe these effects. G. Cappello, LiPhy.

Voir en ligne : Extracellular matrix in multicellular aggregates acts as a pressure sensor controlling cell proliferation and motility. M.E. Dolega, S. Monnier, B. Brunel, J.-F. Joanny, P. Recho, G. Cappello, eLife, Publié le 11 mars 2021.