2026-08-29T15:34:03Zhttps://repisalud.isciii.es/rest/oai/requestoai:repisalud.isciii.es:20.500.12105/230682024-11-29T19:58:48Zcom_20.500.12105_2173com_20.500.12105_2051col_20.500.12105_19597
Repisalud
author
Martínez-Bosch, Neus
author
Fernández-Barrena, Maite G
author
Moreno, Mireia
author
Ortiz-Zapater, Elena
author
Munné-Collado, Jessica
author
Iglesias, Mar
author
André, Sabine
author
Gabius, Hans-Joachim
author
Hwang, Rosa F
author
Poirier, Françoise
author
Navas, Carolina
author
Guerra, Carmen
author
Fernández-Zapico, Martin E
author
Navarro, Pilar
funder
Unión Europea. Fondo Europeo de Desarrollo Regional (FEDER/ERDF)
funder
Instituto de Salud Carlos III
funder
Ligue Nationale Contre le Cancer (Francia)
funder
Fundacio La Marato'TV3
funder
AICR
funder
Generalitat Catalunya
funder
EC GlycoHIT program
funder
Fundacion Ramon Areces
funder
Mayo Clinic Pancreatic SPORE
funder
Mayo Clinic Center for Cell Signaling in Gastroenterology
2024-09-16T08:16:53Z
2024-09-16T08:16:53Z
2014-07-01
Cancer Res . 2014 J;74(13):3512-24.
10.1158/0008-5472.CAN-13-3013
1538-7445
Cancer research
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4332591/pdf/nihms-663468.pdf
24812270
https://hdl.handle.net/20.500.12105/23068
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.
eng
Galectin-1 drives pancreatic carcinogenesis through stroma remodeling and Hedgehog signaling activation.
research article