Researchers review scientific articles on proteins that help cancer cells enter the brain

A team of international scientists, including researchers at the University of Szenov, reviewed scientific articles on proteins (and the genes that encode them) that help cancer cells enter the brain.

Understanding the processes that promote the formation of metastases in the brain enables scientists to create new methods for the diagnosis and treatment of cancer. Details of the study can be found in the journal Cancer tendency..

Brain tissue is very sensitive to changes in the levels of many substances and the penetration of microorganisms and immune cells, but requires large amounts of nutrients and oxygen.

To meet the needs of the brain, we need a dense network of thin blood vessels, encased in a special shell that takes up essential substances and blocks cells from all other compounds.

This shell, composed of adjacent endothelial cells that are intimately connected to each other by specialized proteins, forms the blood-brain barrier (BBB), which prevents free exchange of substances between blood vessels and brain tissue.

BBB works very well (releases less than 2% of the molecule), but is still not perfect. Cancer cells can slip through and trigger the development of metastases. Since many drugs cannot enter the brain, this significantly complicates cancer treatment and worsens the prognosis of patients with metastases. The authors of the article decided to find out which gene confers such “emphasis” to cancer cells.

Metastasis formation is controlled by proteins and the genes that encode these proteins. The purpose of this study was to codify ly or clinically proven findings for proteins and microRNAs that allow tumor cells to migrate to the brain.

Although most of the cell molecules described in the literature are unique to certain types of tumors, their production has been found to be typical of many metastases.

Therefore, the possibility of regulating genes that stimulate the migration of tumor cells into the brain may be a challenge for physicians to reduce the formation of brain metastases in the future,” Ilya Ulasov, one of the authors. , Institute for Regenerative Medicine, University of Szenov.

Tumor cells are known to enter the brain through both intimate contact between the cells of the capsule (the layer of blood vessels) and these cells themselves. In the first case, cancer cells use enzymes and/or microRNAs to disrupt the structure of intimate contacts and enhance BBB permeability.

One of these enzymes is cathepsin C. It destroys close-contact proteins and its inhibitors, substances that slow its action, can suppress the growth of breast cancer metastases.

Two other enzymes-seprase and urokinase-type plasminogen activator-have shown similar effects in melanoma, and some metalloproteinases may be targets for anti-cancer therapy. Another protein, placental growth factor, triggers a series of reactions that promote the development of lung, gastric, or colorectal cancer metastases.

Micro Rna enables communication between cancer cells and their environment, including BBB cells and proteins. For example, miR-105 affects the ZO-1 protein and contributes to the formation of breast cancer metastases, while miR-143-3p can increase lung cancer BBB permeability.

The second method-permeation of cancer cells through BBB cells-is possible due to a specific group of cell wall proteins, integrins, and enzymes. In some types of cancer, metastatic cells showed increased content of integrins avβ3 and avβ8.

They are involved in the formation of metastases in the brain and may serve as biomarkers of disease. Another integrin, VLA-4, is produced in metastases in most melanoma patients and promotes the binding of cancer cells to BBB cells, paving the way for the brain.

Overall, the authors reviewed 44 proteins, described the mechanism of their effect on the formation of metastases, and listed the genes that encode them. This study will help scientists come up with new ways to prevent and treat cancer, stroke, and Alzheimer’s disease, and also affect the integrity of BBB.