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oai:repisalud.isciii.es:20.500.12105/110112024-11-29T19:53:07Zcom_20.500.12105_2173com_20.500.12105_2051col_20.500.12105_19597

00925njm 22002777a 4500 dc Navarro, Rocío author Tapia-Galisteo, Antonio author Martín-García, Laura author Tarín, Carlos author Corbacho, Cesáreo author Sánchez-Tirado, Esther author Campuzano, Susana author González-Cortés, Araceli author Yáñez-Sedeño, Paloma author Compte, Marta author Sanz, Laura author Tapia‐Galisteo, Antonio author Martín‐García, Laura author Gómez-López, Gonzalo author Sánchez‐Tirado, Esther author González‐Cortés, Araceli author Yáñez‐Sedeño, Paloma author Álvarez-Vallina, Luis author 2020-08-07 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. Mol Oncol . 2020 Aug 7. 10.1002/1878-0261.12779 1878-0261 1574-7891 Molecular oncology 32767843 http://hdl.handle.net/20.500.12105/11011 IGFBP-3 TGF-β Colorectal cancer Pericyte Tumor microenvironment TGF-β-induced IGFBP-3 is a key paracrine factor from activated pericytes that promotes colorectal cancer cell migration and invasion.