Researchers have been able to identify how melanoma shapes its environment in order to spread through the body Tel aviv university

2023-05-24 12:43:00

A new study by Tel Aviv University and Sheba Tel Hashomer Medical Center shows for the first time how melanoma cancer cells shape their immediate environment to their needs, when they create new lymphatic vessels in the skin layer (dermis), in order to penetrate deeper into the skin and spread throughout the body. The researchers estimate that the new discovery may later lead to the development of a general vaccine against the deadly cancer.

They cracked the transition to the metastatic stage

The scientific breakthrough was made under the leadership of Prof. Carmit Levy From the Sackler Faculty of Medicine and Prof. Shoshana Greenberger from Sheba Tel Hashomer Medical Center. The results of the study, which was funded by the Israel Cancer Research Fund (ICRF), were published in the Journal of Investigative Dermatology from Nature.

Melanoma, the deadliest skin tumor, begins with the uncontrolled division of melanocytic cells in the epidermis, the top layer of the skin. In the second stage, the cancer cells penetrate into the dermis and metastasize through the lymphatic and blood systems. In previous studies, a dramatic increase in the density of cutaneous lymphatic vessels around the melanoma was observed, in a mechanism that until now was not understood by researchers.

“The main question of the research is to understand how the melanoma affects the formation of the lymphatic vessels, through which it moves to the metastatic stage,” explains Prof. Shoshana Greenberger. “We showed for the first time that in the primary epidermis stage, the melanoma cells secrete vesicles – bubbles – called melanosomes, and we showed that they know how to enter the lymphatic vessels.

Then we tested the behavior of the bubbles also in the vicinity of the lymph cells themselves, and we saw that even there the bubbles know how to penetrate inside the cell and signal the cell to reproduce. In other words, the primary melanoma secretes extracellular bubbles that penetrate the vessels and lymph cells and encourages the formation of vessels and lymph cells near the tumor, which allows the melanoma to become advanced to the stage of fatal metastases.”

Prepares the ground for the metastases

“The melanoma secretes the bubbles of melanosomes before it reaches the dermis layer and thus makes the immediate environment sympathetic towards it. It is actually responsible for the entire dermis being enriched with lymphatic vessels, and prepares the substrate for metastasis. In further research, we prove that the melanosomes do not stop in the lymph cells, but also affect The immune system, for example,” explains Prof. Carmit Levy.

The good news is that understanding the mechanism of the spread of metastases in the lymphatic and blood systems may lead to the development of a general vaccine against the deadly cancer since melanoma is not dangerous in the pre-metastatic stage. “Therefore, the most promising direction in the fight against melanoma is the immunotherapeutic direction: developing a vaccine that will stimulate the immune system to oppose melanosomes, and specifically developing a vaccine that will stimulate the immune system against the lymphatic endothelial cells that the melanosomes have already penetrated. If we know how to stop the mechanisms that create the metastases in the lymph nodes, we will also know how to stop the the spread of the disease”, concludes Prof. Greenberger.

^{They cracked the transition to the metastatic stage. Prof. Carmit Levy and Prof. Shoshana Greenberger}