Citations 2
Targeting galectin-1 inhibits pancreatic cancer progression by modulating tumor–stroma crosstalk
Orozco, Carlos A. , Martínez‐Bosch, Neus , Guerrero, Pedro Enrique , Vinaixa, Judith , Dalotto‐Moreno, Tomás , Iglesias, Mar , Moreno, Mireia , Djurec, Magdolna, Poirier, Françoise, Fernández-Zapico, Martín E. , Hwang, Rosa F. , Guerra, Carmen , Navarro, Pilar , Navarro, Pilar , Gabius, Hans‐Joachim , Rabinovich, Gabriel A
Proceedings of the National Academy of Sciences | April 3, 2018 | Volume: 115 | Issue: 16 | Pages: No page available
Significance Pancreatic ductal adenocarcinoma (PDA) is the third leading of cause of cancer death in the United States and is predicted to be the second one by 2030. The tumor microenvironment is a major source of soluble mediators that influence tumor progression and hinder the success of therapeutic strategies. Using a genetically engineered mouse model and human cell-based systems, we identify galectin-1 (Gal1) as a critical soluble factor capable of regulating tumor–stroma crosstalk promoting proliferation, angiogenesis, and modulation of inflammatory responses, resulting in enhanced tumor development and metastasis. Our data provide an integrated view of the role of Gal1 in the PDA microenvironment and reinforce the high therapeutic value of Gal1 inhibition in PDA treatment.
Galectin-1 Drives Pancreatic Carcinogenesis through Stroma Remodeling and Hedgehog Signaling Activation
Martínez‐Bosch, Neus , Fernández‐Barrena, Maite G. , Moreno, Mireia , Ortíz-Zapater, Elena , Munné‐Collado, Jessica, Iglesias, Mar , André, Sabine , Gabius, Hans‐Joachim , Hwang, Rosa F. , Poirier, Françoise, Navas, Carolina, Guerra, Carmen , Fernández-Zapico, Martín E. , Navarro, Pilar , Navarro, Pilar
Cancer Research | May 9, 2014 | Volume: 74 | Issue: 13 | Pages: 3512-3524
Abstract Despite some advances, pancreatic ductal adenocarcinoma (PDAC) remains generally refractory to current treatments. Desmoplastic stroma, a consistent hallmark of PDAC, has emerged as a major source of therapeutic resistance and thus potentially promising targets for improved treatment. The glycan-binding protein galectin-1 (Gal1) is highly expressed in PDAC stroma, but its roles there have not been studied. Here we report functions and molecular pathways of Gal1 that mediate its oncogenic properties in this setting. Genetic ablation of Gal1 in a mouse model of PDAC (EIa-myc mice) dampened tumor progression by inhibiting proliferation, angiogenesis, desmoplasic reaction and by stimulating a tumor-associated immune response, yielding a 20% increase in relative lifesplan. Cellular analyses in vitro and in vivo suggested these effects were mediated through the tumor microenvironment. Importantly, acinar-to-ductal metaplasia, a crucial step for initiation of PDAC, was found to be regulated by Gal1. Mechanistic investigations revealed that Gal1 promoted Hedgehog pathway signaling in PDAC cells and stromal fibroblasts as well as in Ela-myc tumors. Taken together, our findings establish a function for Gal1 in tumor-stroma crosstalk in PDAC and provide a preclinical rationale for Gal1 targeting as a microenvironment-based therapeutic strategy. Cancer Res; 74(13); 3512–24. ©2014 AACR.