2026-06-14T05:08:10Zhttps://repisalud.isciii.es/rest/oai/requestoai:repisalud.isciii.es:20.500.12105/83592024-11-29T23:55:24Zcom_20.500.12105_2173com_20.500.12105_2051col_20.500.12105_19597
Repisalud
author
Orozco, Carlos A
author
Martinez-Bosch, Neus
author
Guerrero, Pedro E
author
Vinaixa, Judith
author
Dalotto-Moreno, Tomás
author
Iglesias, Mar
author
Moreno, Mireia
author
Djurec, Magdolna
author
Poirier, Françoise
author
Gabius, Hans-Joachim
author
Fernandez-Zapico, Martin E
author
Hwang, Rosa F
author
Guerra, Carmen
author
Rabinovich, Gabriel A
author
Navarro, Pilar
funder
Ministerio de Economía y Competitividad (España)
funder
Unión Europea. Fondo Europeo de Desarrollo Regional (FEDER/ERDF)
funder
Asociación Española de Pancreatologia
funder
Government of Catalonia (España)
funder
Colciencias
funder
University of Buenos Aires (Argentina)
funder
Sales Foundation
funder
Bunge and Born Foundation
funder
National Scientific and Technical Research Council (Argentina)
2019-09-20T11:45:55Z
2019-09-20T11:45:55Z
2018-04-17
Proc Natl Acad Sci U S A. 2018 ;115(16):E3769-E3778.
10.1073/pnas.1722434115
1091-6490
0027-8424
Proceedings of the National Academy of Sciences of the United States of America
29615514
http://hdl.handle.net/20.500.12105/8359
Pancreatic ductal adenocarcinoma (PDA) remains one of the most lethal tumor types, with extremely low survival rates due to late diagnosis and resistance to standard therapies. A more comprehensive understanding of the complexity of PDA pathobiology, and especially of the role of the tumor microenvironment in disease progression, should pave the way for therapies to improve patient response rates. In this study, we identify galectin-1 (Gal1), a glycan-binding protein that is highly overexpressed in PDA stroma, as a major driver of pancreatic cancer progression. Genetic deletion of Gal1 in a Kras-driven mouse model of PDA (Ela-KrasG12Vp53
-/-
) results in a significant increase in survival through mechanisms involving decreased stroma activation, attenuated vascularization, and enhanced T cell infiltration leading to diminished metastasis rates. In a human setting, human pancreatic stellate cells (HPSCs) promote cancer proliferation, migration, and invasion via Gal1-driven pathways. Moreover, in vivo orthotopic coinjection of pancreatic tumor cells with Gal1-depleted HPSCs leads to impaired tumor formation and metastasis in mice. Gene-expression analyses of pancreatic tumor cells exposed to Gal1 reveal modulation of multiple regulatory pathways involved in tumor progression. Thus, Gal1 hierarchically regulates different events implicated in PDA biology including tumor cell proliferation, invasion, angiogenesis, inflammation, and metastasis, highlighting the broad therapeutic potential of Gal1-specific inhibitors, either alone or in combination with other therapeutic modalities.
eng
Galectin-1
Pancreatic cancer
Pancreatic stellate cells
Tumor immunity
Tumor microenvironment
Targeting galectin-1 inhibits pancreatic cancer progression by modulating tumor-stroma crosstalk
journal article
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
URL
https://repisalud.isciii.es/bitstreams/2e23c655-af23-4ab1-9d1e-0902c252e917/download
File
MD5
070a67e0b7568794cd3582c691591776
2492066
application/pdf
Targetinggalectin-1inhibits_2018.pdf
URL
https://repisalud.isciii.es/bitstreams/0c39cf19-b2b7-4d1a-9a81-cea1d17de706/download
File
MD5
dd735f680cc35ade088aa9dda3b211db
1211677
application/pdf
Targetinggalectin-1inhibits_supl_2018.pdf
URL
https://repisalud.isciii.es/bitstreams/88301574-c307-487b-89e0-ab3dc785d6d9/download
File
MD5
cef931d11f4cdb6c2284fcf120b5eac4
3027968
application/vnd.ms-excel
Targetinggalectin-1inhibits_dataset_2018.xls
URL
https://repisalud.isciii.es/bitstreams/b277374b-2d48-4bd0-bd6a-413835bae34b/download
File
MD5
f809d8ff672f660e10e643fc4bde5057
67719
text/plain
Targetinggalectin-1inhibits_2018.pdf.txt
URL
https://repisalud.isciii.es/bitstreams/ecdaa9ea-16a7-4ac3-ac2d-76de3732d12b/download
File
MD5
af03deac71091a9ce831e02ed996b542
10110
text/plain
Targetinggalectin-1inhibits_supl_2018.pdf.txt
URL
https://repisalud.isciii.es/bitstreams/e46317db-39ef-427f-9adb-3736b200ae87/download
File
MD5
be260f8fcb645251f9c50f2e79e8ccaa
100006
text/plain
Targetinggalectin-1inhibits_dataset_2018.xls.txt