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2025-10-01

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cc-by-nc-nd (c) Recalde Percaz, Leire et al., 2025
Si us plau utilitzeu sempre aquest identificador per citar o enllaçar aquest document: https://hdl.handle.net/2445/224773

Neuropilin-2 upregulation by stromal TGFβ1 induces lung disseminated tumor cells dormancy escape and promotes metastasis outgrowth

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https://doi.org/10.1016/j.neo.2025.101220

Resum

Metastasis is the main cause of death from solid tumors. Therefore, identifying the mechanisms that govern metastatic growth poses a major biomedical challenge. Tumor microenvironment signals regulate the fate and survival of disseminated tumor cells (DTCs) in secondary organs. However, very little is known about the role of nervous system mediators in this process. We have previously reported that neuropilin-2 (NRP2) expression in breast cancer correlates with poor prognosis. Here, we show that NRP2 positively regulates the proliferation, invasion, and survival of breast and head and neck cancer cells in vitro. NRP2 deletion in tumor cells inhibits tumor growth in vivo and decreases the number and size of lung metastases by promoting lung DTCs quiescence. NRP2 deletion upregulates dormancy and cell cycle regulators expression and promotes DTCs reprograming into quiescence. Moreover, lung fibroblasts and macrophages induce NRP2 upregulation in DTCs through the secretion of TGFβ1. NRP2 facilitates lung DTC interaction with the extracellular matrix and promotes lung DTCs activation and metastasis. Therefore, we conclude that the TGFβ1-NRP2 axis is a new key dormancy-awakening inducer that promotes DTCs proliferation and lung metastasis development.

Matèries

Càncer de mama, Càncer de cap, Càncer de coll, Metàstasi

Matèries (anglès)

Breast cancer, Head cancer, Neck cancer, Metastasis

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Articles publicats en revistes (Biomedicina)
Articles publicats en revistes (Institut de Biomedicina (IBUB))

Citació

RECALDE PERCAZ, Leire, DE LA GUÍA LÓPEZ, Inés, LINZOAIN-AGOS, Paula, NOGUERA CASTELLS, Aleix, RODRIGO-FAUS, María, JAUREGUI, Patricia, LÓPEZ PLANA, Anna, FERNÁNDEZ NOGUEIRA, Patricia, INIESTA-GONZÁLEZ, Minerva, CUETO-REMACHA, Mateo, MANZANO, Sara, ALONSO, Rodrigo, MORAGAS, Núria, BAQUERO, Cristina, PALAO, Nerea, DALLA, Erica, AVILÉS JURADO, Francesc xavier, VILASECA GONZÁLEZ, Isabel, LEON VINTRO, Xavier, CAMACHO, Mercedes, FUSTER ORELLANA, Gemma, ALCARAZ CASADEMUNT, Jordi, AGUIRRE-GHISO, Julio, GASCÓN, Pere, PORRAS, Almudena, GUTIÉRREZ-UZQUIZA, Álvaro, CARBÓ CARBÓ, Neus, BRAGADO DOMINGO, Paloma. Neuropilin-2 upregulation by stromal TGFβ1 induces lung disseminated tumor cells dormancy escape and promotes metastasis outgrowth. _Neoplasia_. 2025. Vol. 68, núm. 1-16. [consulta: 28 de gener de 2026]. ISSN: 1476-5586. [Disponible a: https://hdl.handle.net/2445/224773]

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