TGF‐β‐induced IGFBP‐3 is a key paracrine factor from activated pericytes that promotes colorectal cancer cell migration and invasion

Navarro, Rocío; Tapia‐Galisteo, Antponio; Martín García, Laura; Tarín, Carlos; Corbacho, Cesáreo; Gómez‐López, Gonzalo; Sánchez Tirado, Esther; Campuzano Ruiz, Susana; González Cortés, Araceli; Yáñez-Sedeño Orive, Paloma; Compte, Marta; Álvarez‐Vallina, Luis; Sanz, Laura

TGF‐β‐induced IGFBP‐3 is a key paracrine factor from activated pericytes that promotes colorectal cancer cell migration and invasion

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Official URL

https://doi.org/10.1002/1878-0261.12779

Publication date

2020

Authors

Navarro, Rocío

Tapia‐Galisteo, Antponio

Martín García, Laura

Tarín, Carlos

Corbacho, Cesáreo

Gómez‐López, Gonzalo

Sánchez Tirado, Esther

Campuzano Ruiz, Susana

González Cortés, Araceli

Yáñez-Sedeño Orive, Paloma

Publisher

Wiley

Citations

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URI

https://hdl.handle.net/20.500.14352/98609

Citation

R. Navarro, A.Tapia-Galisteo, L.Martín-García, C. Tarín, C. Corbacho, G. Gómez-López, E. Sánchez-Tirado, S. Campuzano, A. González-Cort és, P. Yáñez-Sedeño, M. Compte, L. Álvarez-Vallina, L. Sanz. Molecular Oncology14(2020) 2609–2628

Abstract

The crosstalk between cancer cells and the tumor microenvironment has been implicated in cancer progression and metastasis. Fibroblasts and immune cells are widely known to be attracted to and modified by cancer cells. However, the role of pericytes in the tumor microenvironment beyond endothelium stabilization is poorly understood. Here, we report that pericytes promoted colorectal cancer (CRC) cell proliferation, migration, invasion, stemness, and chemoresistance in vitro, as well as tumor growth in a xenograft CRC model. We demonstrate that coculture with human CRC cells induced broad transcriptomic changes in pericytes, mostly associated with TGF‐β receptor activation. The prognostic value of a TGF‐β response signature in pericytes was analyzed in CRC patient data sets. This signature was found to be a good predictor of CRC relapse. Moreover, in response to stimulation by CRC cells, pericytes expressed high levels of TGF‐β1, initiating an autocrine activation loop. Investigation of secreted mediators and underlying molecular mechanisms revealed that IGFBP‐3 is a key paracrine factor from activated pericytes affecting CRC cell migration and invasion. In summary, we demonstrate that the interplay between pericytes and CRC cells triggers a vicious cycle that stimulates pericyte cytokine secretion, in turn increasing CRC cell tumorigenic properties. Overall, we provide another example of how cancer cells can manipulate the tumor microenvironment.