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Molecular Oncology Programme

Microenvironment & Metastasis Group

Group Leader:  Hector Peinado
Research highlights
Decoding tumour-microenvironment communication in metastasis

Tumour-secreted extracellular vesicles constitute a network of communication secreted by primary tumours favouring metastasis. In melanoma, tumour-adjacent lymph nodes (a.k.a. sentinel lymph nodes) are normally the first sites of metastasis. In this project, we are focused on unravelling the role of tumourderived exosomes as entities promoting cellular and molecular alterations in the lymph node microenvironment, facilitating metastasis (FIGURE). In particular, we are investigating the effects of tumour exosomes in the lymphatic vasculature. In addition, we are developing nanoparticles (FIGURE B, left panel) as sensors of pre-metastatic niches mimicking tumour-derived exosomes (FIGURE B, right panel) that will help to identify future areas of metastasis. These studies will lead to the development of novel technologies and therapies to block metastatic disease.

Fatal triage: adipose tissue, coagulation and metastasis

Over the past few decades, the incidence of overweight and obesityhas been increasing very rapidly in both developed and developingcountries, making obesity one of the most serious health problemsworldwide. Increasing evidences have revealed a link betweenobesity and the development of certain types of cancer; still theimpact of obesity on metastasis is not well established. Recent datasupport a role for secreted factors [e.g. soluble factors and EVs]in the communication between tumour cells and adipose tissueduring tumour metastasis. In this project, we are investigatingthe local crosstalk between the adipose tissue and tumour cells, analysing secreted factors and EVs as well as the role of platelets as systemic players in the metastatic process.

Testing new therapies to prevent metastasis

Neurofibromatosis type 1 (NF1) is a genetic disorder which can progress to Malignant Peripheral Nerve Sheath Tumour (MPNST), a highly aggressive sarcoma. In this project, we are analysing the main pathways involved in tumour- microenvironment crosstalk during metastatic progression. In order to find potential biomarkers and candidates to target the progression of the disease, we investigated the molecular signature of exosomes secreted by MPNST cell lines. We have identified several candidates and we are currently performing a multidrug screening in combination with these markers in order to find new therapies for the treatment of this disease.