RT Journal Article
T1 TGF‐β‐induced IGFBP‐3 is a key paracrine factor from activated pericytes that promotes colorectal cancer cell migration and invasion
A1 Navarro, Rocío
A1 Tapia‐Galisteo, Antponio
A1 Martín García, Laura
A1 Tarín, Carlos
A1 Corbacho, Cesáreo
A1 Gómez‐López, Gonzalo
A1 Sánchez Tirado, Esther
A1 Campuzano Ruiz, Susana
A1 González Cortés, Araceli
A1 Yáñez-Sedeño Orive, Paloma
A1 Compte, Marta
A1 Álvarez‐Vallina, Luis
A1 Sanz, Laura
AB 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.
PB Wiley
SN 1574-7891
YR 2020
FD 2020
LK https://hdl.handle.net/20.500.14352/98609
UL https://hdl.handle.net/20.500.14352/98609
LA eng
NO 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
NO Comunidad de Madrid
NO Ministerio de Economía y Competitividad (España)
NO European Commission
NO Instituto de Salud Carlos III
DS Docta Complutense
RD 29 sept 2024