Study Group of the Institute of Biomedical Research sarcoma Bellvitge (IDIBELL) led by Dr. Oscar Martinez-triad identified a potential new therapeutic target for Ewing's sarcoma, the second frequency of bone cancer in children and adolescents, and tumors, known for their aggressiveness and propensity to metastasize. The study is published in the International Journal of Cancer.
For many years, the main line of the group of Ewing's sarcoma research has focused on the protein caveolin 1 (CAV1), which is associated with resistance to treatment and metastasis, among other problems. However, the location of the protein within the cell makes its use as a therapeutic target practically impossible. "Therefore, we are looking for a cofactor CAV1 with an equally important role, but a more affordable place, - says Dr. Martinez-Tirado - and membrane receptor EphA2, already described in previous studies, meets these requirements."
In his latest work, the researchers not only to demonstrate the connection between the receptor EphA2 and caveolin 1, but also to establish a correlation between EphA2 phosphorylation and tumor aggressiveness in Ewing's sarcoma. "In a few tests in vitro and in vivo, we observed that the membrane receptor plays a key role in tumor cell migration."
With regard to research in vivo, the research team used two different models. Artificial metastasis model, a pilot, allowing researchers to assess the ability of cells to adhere to lung epithelium in adverse conditions. On the other hand, the new orthotopic model, designed by the same group a few months ago, induces spontaneous metastases, similar to what can be observed in the clinical setting.
"In the laboratory, we have shown that the lack of EphA2 receptor significantly reduces the frequency and number of metastases, - says Dr. Martinez-Tirado - and thanks to the cooperation with the hospital Virgen del Rocío, we saw that 90 percent of patients with Ewing's sarcoma, this receptor is expressed (simulates caveolin 1 ), which is a fundamental fact, when it comes to choosing the EphA2 as a therapeutic target. At the same time work with the patients samples allowed us to compare the activity of ligand-independent EphA2, related to its phosphorylation, a lower survival rate. "
Thanks to the stable financial support Alba Perez Foundation IDIBELL researchers continue to work on the development of therapies based on blocking this receptor activity. "With nanoinzhenernogo treatments we aim to design a molecule with a double effect, capable of blocking EphA2 in tumor cells and simultaneously deliver other targeted drugs," - concludes IDIBELL researcher.