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2022-02-22

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Si us plau utilitzeu sempre aquest identificador per citar o enllaçar aquest document: https://hdl.handle.net/2445/207366

Stromal Oncostatin M cytokine promotes breast cancer progression by reprogramming the tumour microenvironment

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https://doi.org/10.1172/JCI148667

Resum

The tumor microenvironment (TME) is reprogrammed by cancer cells and participates in all stages of tumor progression. The contribution of stromal cells to the reprogramming of the TME is not well understood. Here, we provide evidence of the role of the cytokine oncostatin M (OSM) as central node for multicellular interactions between immune and nonimmune stromal cells and the epithelial cancer cell compartment. OSM receptor (OSMR) deletion in a multistage breast cancer model halted tumor progression. We ascribed causality to the stromal function of the OSM axis by demonstrating reduced tumor burden of syngeneic tumors implanted in mice lacking OSMR. Single-cell and bioinformatic analysis of murine and human breast tumors revealed that OSM expression was restricted to myeloid cells, whereas OSMR was detected predominantly in fibroblasts and, to a lower extent, cancer cells. Myeloid-derived OSM reprogrammed fibroblasts to a more contractile and tumorigenic phenotype and elicited the secretion of VEGF and proinflammatory chemokines CXCL1 and CXCL16, leading to increased myeloid cell recruitment. Collectively, our data support the notion that the stromal OSM/OSMR axis reprograms the immune and nonimmune microenvironment and plays a key role in breast cancer progression.

Matèries

Càncer de mama, Tumors, Cèl·lules canceroses

Matèries (anglès)

Breast cancer, Tumors, Cancer cells

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Articles publicats en revistes (Biomedicina)

Citació

ARAUJO, Ángela m., ABAURREA, Andrea, AZCOAGA, Peio, LÓPEZ VELAZCO, Joanna i., MANZANO, Sara, RODRÍGUEZ, Javier, REZOLA, Ricardo, EGIA MENDIKUTE, Leire, VALDÉS MORA, Fátima, FLORES, Juana m., JENKINS, Liam, PULIDO, Laura, OSORIO QUEREJETA, Iñaki, FERNANDEZ-NOGUEIRA, Patricia, FERRARI, Nicola, VIERA, Cristina, MARTIN MARTIN, Natalia, TZANKOV, Alexandar, EPPENBERGER CASTORI, Serenella, ALVAREZ LOPEZ, Isabel manuela, URRUTICOECHEA RIBATE, Ander, BRAGADO DOMINGO, Paloma, COLEMAN, Nicholas, PALAZÓN, Asis, CARRACEDO, Arkaitz, GALLEGO ORTEGA, David, CALVO, Fernando, ISACKE, Clare m., CAFFAREL, María m., LAWRIE, Charles h.. Stromal Oncostatin M cytokine promotes breast cancer progression by reprogramming the tumour microenvironment. _Journal of Clinical Investigation_. 2022. Vol. 132, núm. 19. [consulta: 29 de gener de 2026]. ISSN: 0021-9738. [Disponible a: https://hdl.handle.net/2445/207366]

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