Galectin-1 is a novel therapeutic target and diagnostic/prognostic biomarker for pancreatic cancer

Abstract

Background: Pancreatic ductal adenocarcinoma (PDA) is one of the most lethal tumor types, with extremely low survival rates due to late diagnosis and resistance to standard therapies. Identification of new molecular targets and biomarkers is therefore an urgent need to improve this pessimistic scenario. Here we analyze the potential use of galectin-1 (Gal1), a glycan-binding protein that is highly overexpressed in PDA stroma, as therapeutic target and biomarker for PDA. Methods: To study the potential use of Gal1 as therapeutic target, effects of Gal1 inhibition has been tested using genetically engineered mouse models (Gal1 knockout mice and a KRas-driven mouse model of PDA) and a human cell-based system. To analyze whether Gal1 can be used as PDA biomarker, its levels were determined by ELISA in plasma from healthy controls and patients diagnosed with PDA, using three independent cohorts Results: Both in mouse models and in a human setting, inhibition of Gal1 leads to impaired tumor formation and metastasis, through modulation of multiple events including proliferation, angiogenesis and immune response. In addition, we found that plasma Gal-1 levels were significantly increased in PDA patients as compared to controls and that high levels of Gal-1 were associated with lower survival in patients with non-resected tumors. Conclusions: Gal1 plays a key role in PDA development and progression, highlighting the high therapeutic value of Gal1 inhibition in PDA treatment. Moreover, detection of Gal1 circulating levels shows a strong potential to be used as a novel biomarker for detection and prognostics of PDA patients.