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Targeting extracellular vesicle mediated intercellular communication: a rational approach for the treatment of cancer metastasis

21st national competition for scientific and technical research

Intercellular Dialogue and Interactome: Pathological Implications

Senior Researcher : Santiago Ramón y Cajal Agueras

Research Centre or Institution : Institut de Recerca Vall d’Hebron


This project focuses on the study of intercellular communication in the development of metastases which account for 90% of cancer associated deaths.

EIn recent years, we have studied tumor formation and metastasis and provide data on the relevance of intercellular communication between tumor cells and with cells of the microenvironment. In this regard, we discovered that integrin beta3, together with heparansulfate glycoproteins (HSPGS), is crucial for extracellular vesicle uptake and vesicle induced colony formation in vitro and for the generation of metastases in mice models. In this project we will focus on the inhibition of exosome uptake via beta3 integrin and HSPGS. We will study the inhibition of intercellular communication by the use of antibodies against different integrin domains, as well as a peptide that blocks uptake of exosomes via HSPGs. Studies on the effect of these inhibitors on the development of cancer metastasis will be carried out in preclinical mice models in vivo. We will furthermore combine this inhibitors with clinically relevant protocols like chemotherapy, radiotherapy or immunotherapy which depend on the tumor type and staging.

Moreover, the expression of the proposed target proteins will be confirmed in a series of patients with metastatic disease to verify the clinical relevance of these proteins.

Based on the obtained data, we aim at proposing new approaches for the treatment of cancer and metastases via the inhibition of intercellular communication and the inhibitors validated in this study.

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