Resumen de Role of galectin-1 in pancreatic cancer stroma, a small but mischievous protein with a novel nuclear function
Pancreatic ductal adenocarcinoma (PDA) is one of the most aggressive tumors and it is predicted to become the second cause of cancer related deaths by 2030. This is mostly due to its lack of symptoms, resulting in late diagnosis, and also to the presence of an aggressive tumor microenvironment, which favors the resistance to current and emerging therapies. Galectin-1 (Gal-1), a glycan-binding protein highly expressed in the PDA stromal compartment, exerts a crucial role in modulating tumor-stroma crosstalk in this disease. In particular, our group has demonstrated that Gal-1 promotes tumor proliferation, metastasis, angiogenesis and immune evasion in PDA. Importantly, Gal-1 is mainly produced by PDA stellate cells (PSC), however the intrinsic role of this protein in PSC biology is poorly understood. In the present study, we define a novel role of endogenous Gal-1 in the biology of pancreatic cancer stroma using a combination of assays in Human PSC (HPSC) models. We determine the impact of Gal-1 in HPSC proliferation, migration, invasion, activation and extracellular matrix organization. Using high throughput analysis (microarrays), we have defined the molecular mechanisms underlying Gal-1 functions in HPSC. Finally, considering that Gal-1 is highly expressed in HPSC nuclei, we elucidate the involvement of nuclear Gal-1 in the regulation of gene expression in these cells.
