When cancer cells break away from a primary tumor and migrate to other organs, this is called metastatic cancer. The organs affected by these metastases, however, depend in part on their tissue of origin. In the case of breast cancerusually form in the bones. In an attempt to identify what determines the organs affected by metastasis, a team from the University of Geneva (UNIGE), in collaboration with researchers from the ETH in Zurich (Switzerland), has identified a implicated protein in this phenomenon.
This discovery, which has been published in the journal ‘Nature Communications’, could lead to the development of therapeutic approaches for suppress metastasis. This study confirms the importance of the plasticity of tumor cells during the metastatic process and could allow, in the long term, to consider new therapeutic approaches to prevent the appearance of metastasis.
From the primary site of a tumor, cancer cells they can invade your microenvironment and then circulate through blood and lymphatic vessels to healthy tissues distant to form metastases. In the case of metastatic breast cancer, cancer cells colonize mainly the bonesbut can also be found in other organs such as the liverlos lungs or the brain.
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Although the molecular and cellular mechanisms responsible for the different stages of the metastatic process are not yet fully understood, studies show that cell plasticity plays an important role. This term refers to the capacity of cells for change function and/or form. Thus, tumor cells that become metastatic change shape and they become mobile.
The laboratory of Professor Didier Picard of the Department of Molecular and Cellular Biology of the Faculty of Sciences is interested in the mechanisms that govern the metastatic processes related to breast cancer. His group collaborated with Professor Nicolás Aceto’s group at ETHZ to study these processes in mice. Biologists investigated the potential role of ZEB1 proteinknown to increase cell plasticityin the migration of breast cancer cells.
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“Unlike women, mice transplanted with human breast cancer cells develop metastases in the lungs, not in the bones. Therefore, we sought to identify factors capable of inducing metastasis in bone tissue and, in particular, we tested the effect of the ZEB1 factor,” says Nastaran Mohammadi Ghahhari, a researcher at the Department of Molecular and Cellular Biology and first author of the study.
In in vitro migration and invasion experiments, the scientists found that cancer cells expressing ZEB1 moved into bone tissue, unlike cancer cells that did not. These results were later confirmed when transplanted human breast cancer cells to the mammary glands mice. If the cancer cells did not express ZEB1, metastasis occurred mainly in the lungs.
In contrast, when ZEB1 was present, bone metastases also developed, as is the case in women. “Therefore, we can assume that this factor is expressed during tumor formation and that it directs the cells that have acquired metastatic features to bone”explains Didier Picard, the last author of the study.
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