The Soengas Group has just reported a paper in Nature
30.06.2017 - Dr. Soengas’ lab deciphers new routes of metastases in melanoma through the lymph vessels with the help of a new set of animal models termed “MetAlert” mice
30.06.2017 - One of the interests of the Melanoma Group at the Spanish National Cancer Research Center (CNIO) is to define the contribution of the lymphatic vasculature to melanoma progression. In particular, whether (and how) the formation of new lymphatic vessels (called lymphangiogeneis) contributes to the ability of melanoma cells to disseminate to multiple organs.
Dr. Marisol Soengas and Dr. David Olmeda
To date, neo-lymphangiogenesis has been studied mainly in the context of the primary tumors or the draining lymph nodes. How tumors are able to modify distal organs remain unclear, in part, because there were no animal models for whole-body imaging and analysis of neo-lymphangiogenesis. The Soengas Group has just reported a paper in Nature (Olmeda et al. 2017), the first-in-class bioluminescent reporter mice for lymphangiogenis. These mice light up when abnormal processes of generation of lymphatic vessels are initiated, something that happens in many metastases. With these mice, the Soengas group has been able to follow how melanomas progress in vivo, identifying pre-metastatic niches before melanoma cells can actually colonize them. By these features, these Vegfr3-luciferase reporter has been termed “MetAlert” mice.
Olmeda and colleagues next identified tumour-secreted factors that promote distant lymphangiogenesis and metastasis. The authors focused on the heparin-binding protein MIDKINE (MDK), which has been shown to mediate metastatic progression in other systems, but was never linked before to lymphangiogenesis or to melanoma. The authors demonstrated that MDK overexpression converted a non-lymphangiogenic melanoma into a potent driver of systemic lymphangiogenesis, resulting in metastases at distal organs. Remarkably, these results obtained with the “MetAlert” mice were validated in human biopsies, where MDK levels correlated with more advanced stages of melanoma.
Two ESR fellows from the Immutrain Consortia, Marta Contreras-Alcalde and Xavier Catena, have participated in this groundbreaking work.
This work has received ample national and international coverage in a multitude of media. Reports included a Nature News & Views by Ayuko Hoshino and David Lyden (Weill Cornell Medicine, USA). These authors concluded that “this work might open a door to diagnostic and therapeutic strategies that aim to deal with metastases before they have a chance to arise”.
