MADRID, 23 Abr. (EUROPA PRESS) –
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 cancer, they usually 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 protein involved in this phenomenon.
This discovery, which has been published in the journal Nature Communications, could lead to the development of therapeutic approaches to 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 can invade its microenvironment and then circulate through blood and lymphatic vessels to distant healthy tissues to form metastases. In the case of metastatic breast cancer, the cancer cells mainly colonize the bones, but can also be found in other organs such as the liver, lungs or brain.
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 ability of cells to change function and/or form. Thus, tumor cells that become metastatic change shape and 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. The biologists investigated the potential role of the ZEB1 protein, known to increase cell plasticity, in the migration of breast cancer cells.
“Unlike women, mice transplanted with human breast cancer cells develop metastases in the lungs, not in the bones. We therefore sought to identify factors capable of inducing metastases in bone tissue and, in particular, 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 human breast cancer cells were transplanted into the mammary glands of 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 characteristics to the bone”, explains Didier Picard, the last author of the study.
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