Metastasis is a negative turning point in the progression of all types of cancer. It means the spread of cancer cells from their place of origin to the bloodstream, from where they can colonise other organs, forming new tumours. It is the main cause of death in cancer patients and, for this reason, a large part of biomedical research is aimed at understanding the molecular mechanisms that make it possible in order to try to prevent it, stop it or remission once it has begun.
This is one of the main interests of the TFG-Beta and Cancer group of the Oncobell Programme of the Bellvitge Biomedical Research Institute (IDIBELL), which has recently published two studies led by Dr. Àngels Fabra that delve into the molecular and cellular mechanisms involved in the development of metastasis in melanomas. In both cases, IDIBELL researchers have collaborated with specialized groups of the Carlos III Health Institute and the University Hospital of Bellvitge, and have focused their research on melanomas. Melanomas are a type of cancer that affects melanocytes, melanin-producing cells, and are characterised by their aggressiveness and ease of generating metastasis.
On the one hand, in collaboration with Dr. Josep Ramon Ferreres and Dr. Joaquim Marcoval from the University Hospital of Bellvitge and Dr. Susana Puig’s group from the Hospital Clínic de Barcelona, IDIBELL’s researchers have published a study in Molecular Oncology in which they have defined the role of the PRRX1 protein during metastasis. Normally, in other types of cancer, PRRX1 has been shown to facilitate epithelial-mesenchymal transition (EMT), a process by which cancer cells undergo a series of changes and gain mobility, increasing their invasive and migratory capacity. However, Dr Fabra’s team has seen that, in malignant cutaneous melanomas, while PRRX1 expression is high in primary tumours that have not metastasised, in invasive melanomas the protein loses expression and is no longer useful.
This is likely explained by the fact that the invading cells have already reached a new target organ where they can replicate the initial tumour and do not need to move, but anchor themselves. This is corroborated by the results obtained, in which the researchers theorise that switching PRRX1 activity from ‘on’ to ‘off’ favours the proliferation of cancer cells at the site of metastasis, promoting the development of metastasis, and is associated with reduced survival of cutaneous melanoma patients.
On the other hand, in the second study, conducted in collaboration with Dr. Josep M Caminal and Dr. Daniel Lorenzo of the University Hospital of Bellvitge, and published in Cancers, the focus has shifted to the study of metastasis in uveal or ocular melanoma, a rare form of melanoma with a high tendency to metastasize to the liver. In this case, the IDIBELL team has elucidated the role of exosomes in the construction of optimal conditions in the liver for the reception of cancer cells during the metastatic process. Exosomes are vesicles, loaded with specific molecular content (proteins, DNA, lipids), which cells expel into the environment and use to communicate with each other. Researchers have studied the protein load of those exosomes released by primary ocular melanoma tumour cells, and have seen how these small vesicles contribute to the migration of tumour cells and especially to the preparation of the pre-metastatic niche in the liver.
In short, both studies have demonstrated the enormous plasticity of cancer cells, which are capable of altering both gene expression and the tumour microenvironment to ensure metastasis. This information is of great value, since knowing the mechanisms by which cells can configure these changes is crucial to stop them and, therefore, is essential for the design of future therapeutic and diagnostic strategies.
The Bellvitge Biomedical Research Institute (IDIBELL) is a biomedical research center created in 2004. It is participated by the Bellvitge University Hospital and the Viladecans Hospital of the Catalan Institute of Health, the Catalan Institute of Oncology, the University of Barcelona and the City Council of L’Hospitalet de Llobregat.
IDIBELL is a member of the Campus of International Excellence of the University of Barcelona HUBc and is part of the CERCA institution of the Generalitat de Catalunya. In 2009 it became one of the first five Spanish research centers accredited as a health research institute by the Carlos III Health Institute. In addition, it is part of the “HR Excellence in Research” program of the European Union and is a member of EATRIS and REGIC. Since 2018, IDIBELL has been an Accredited Center of the AECC Scientific Foundation (FCAECC).