Glycomedicine

Galectins and cancer

Galectins are proteins that recognize specific sugars in cells and thus trigger or modulate a biological response.
Our laboratory was a pioneer in showing that, through its interaction with specific sugars, Galectin-1 can inhibit the immune response and promoting processes that lead to tumor progression to metastasis.
We further demonstrate that tumor cells use Galectin-1 for the purposes of inhibiting the antitumor immune response and inducing immune system evasion. In this sense, Galectin-1 has been involved in the development of various types of cancer, and its expression or overexpression in tumor tissues is a sign of malignant progression and poor prognosis.
Our team studies these interactions between galectins and glycans in various tumor types such as: breast cancer, lung cancer, kidney cancer, melanoma, colorectal cancer, and chronic lymphocytic leukemia (CLL).
Breast cancer is a very common disease, one in 8 women will suffer from it throughout her life. Although early detection and advances in targeted therapies make patient survival high, new strategies to treat metastatic or disseminated disease have yet to be discovered. Our breast cancer team is particularly dedicated to studying how the interactions between Galectin-1 and the sugars found on the tumor cell can affect tumor progression and metastasis. We mainly study the role of Galectin-1, produced by the tumor or by the tumor microenvironment, from two fundamental approaches. On the one hand, we evaluated whether Galectin-1 can stop the antitumor immune response by binding to the cells of our defense system, and on the other we analyzed whether Galectin-1 is itself mediating invasion and metastasis by acting on cells of the tumor.
In particular, in melanoma, lung and kidney cancer, we are working on deciphering the mechanisms that mediate the resistance of these tumors to the most widely used immunotherapies such as immune checkpoint blockade antibodies (anti PD-1 or anti PD-L1). We have established animal models that reproduce human pathology and allow us to study these mechanisms in detail.

Galectin-1 and tumor angiogenesis

Our work set the bases to explain a new mechanism of resistance to antiangiogenic therapy based on the interaction between Galectin-1 (Gal-1) and glycans present on the surface of endothelial cells that form blood vessels. In 2014 we published a paper in the renowned scientific journal “”Cell”” where we demonstrated that tumors resistant to antiangiogenic therapy with Bevacizumab could modify the glycan profile on the surface their endothelial cells, allowing the adhesion of Gal-1 and generating new blood vessels. This resulted in the lack of response of antiangiogenic therapy, thus inhibiting the effectiveness of anti-VEGF treatment. On the other hand, we show that tumoral Gal-1 not only promotes this resistance to antiangiogenic therapy, but also inhibits the immune response against tumors.
This dual effect of Galectin-1 allows a homeostatic regulation mechanism in both systems.