Vall d'Hebron identifies a key protein to prevent breast cancer metastases

Integrin B3 allows the uptake of vesicles that carry signaling factors in tumor cells, which favor the spread of the tumor in other organs, such as the lungs.

08/09/2020

A team of researchers from the Translational Molecular Pathology group from Vall d’Hebron Institute of Research (VHIR) in collaboration with CIBER of Cancer (CIBERONC) has described the role of integrin B3 protein (ITGB3) in the metastasis of breast cancer. The study, published in Nature Communications, shows the importance of integrin B3 in the uptake of vesicles by cells, which favors the formation of secondary tumors in other organs such as the lungs. Thus, this protein would be a therapeutic target to prevent metastasis formation.

90% of deaths caused by breast cancer are due to metastasis in other organs, such as the lungs. For these metastases to occur, communication between tumor cells and also with cells in the metastatic site environment is key. This cellular communication is based on the production of vesicles that are taken up by other cells and that contain factors that help to develop metastases. However, the mechanism that allows this to happen is not fully understood. “This is one of the first studies that describe the pathways that allow these vesicles to enter inside the cells to promote tumor growth and the role that integrin B3 plays in this process have been studied”, explains Dr. Stefan Hümmer, researcher in the Translational Molecular Pathology group at VHIR and at CIBER and one of the authors of the work.

The study, carried out in cell cultures in the laboratory, has verified that B3 integrin, a protein that serves as a connection between the outside and the inside part of the cell, is necessary for the vesicles produced by the environment to be taken up by the tumor cells. “We have seen that, when we inhibit integrin B3, vesicles cannot be internalized and, therefore, there is no stimulus that favors tumor growth in the new organ to form metastasis”, comments Dr. Santiago Ramon y Cajal, head of the Translational Molecular Pathology group at VHIR, head of the Pathological Anatomy Department at Vall d’Hebron University Hospital and head of group at CIBERONC.

This work is the continuation of other previous studies where it has been observed that integrin B3 increases when there is oxygen deprivation and favors cell migration and metastasis. Following this publication, the group is working on the search for inhibitors of integrin B3, which would be a possible strategy to prevent cells from forming new colonies in other organs, that is, to avoid metastasis. Therefore, Dr. Ramon y Cajal emphasizes that “these inhibitors would be specific for the control of metastases. For this reason, they should be administered in conjunction with other treatments directed at the primary tumor”.

This mechanism of entry into cells, based on integrin B3, has previously been observed in many herpes viruses when they infect human cells. These similarities have helped researchers to understand and study the entry pathway of vesicles.

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