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Cancer cells, working towards new therapeutic approaches

18.02.2022

Paving the way for new therapeutic approaches in cancer, the study entitled Mitochondrial fission links ECM mechanotransduction to metabolic redox homeostasis and metastatic chemotherapy resistance was published in the journal Nature Cell Biology by an international research group coordinated by Sirio Dupont of the Department of Molecular Medicine of the University of Padua.

The research shows what happens when breast cancer cells migrate from the primary site to the lung during the process that leads to metastasis.

The research team studied the mechanisms that cause this response, which appears to be a shift towards the shortening of the mitochondria in response to its soft microenvironment. This shortening, through a complex chain of molecular events, stimulates the cells to produce a large number of antioxidant molecules. This follows with cancer cells becoming resistant to some forms of chemotherapy. Experiments conducted on laboratory animal models have shown that by depriving metastatic cells of this response, such as elongating the mitochondria, the models become sensitive to chemotherapy and prevent relapse.

Researcher Patrizia Romani explains, "We observed that the stiffening of the primary tumour microenvironment promotes tumour growth, but when cancer cells migrate to tissues such as lungs, they find themselves in a soft environment. We know that the mechanical properties of tissues can regulate the behaviour of cells, including cancer cells. We have found that when the metastatic site softness the growth of metastatic cells slows down and its antioxidant defences increases This accounts for the fact that lung metastases are often resistant to chemotherapy and can remain dormant for many years until they relapse."

The study was made possible thanks to the Worldwide Cancer Research, the Veronesi Foundation and the AIRC Foundation and the collaboration of numerous research groups - The University of Padua Departments of Biology, Biomedical Sciences, Surgical and Oncological Sciences, Industrial Engineering, the Veneto Institute of Molecular Medicine, Veneto Oncology Institute, University College of London, and the Queen's University of Kingston in Canada.