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Functional heterogeneity of cancer-associated fibroblasts from human colon tumors shows specific prognostic gene expression signature

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Herrera, Mercedes & Islam, Abul B M M K & Herrera, Alberto & Martín, Paloma & García, Vanesa & Silva, Javier & Garcia, Jose M & Salas, Clara & Casal, Ignacio & García de Herreros, Antonio & Bonilla, Félix & Peña, Cristina .Functional heterogeneity of cancer-associated fibroblasts from human colon tumors shows specific prognostic gene expression signature.

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Herrera, Mercedes & Islam, Abul B M M K & Herrera, Alberto & Martín, Paloma & García, Vanesa & Silva, Javier & Garcia, Jose M & Salas, Clara & Casal, Ignacio & García de Herreros, Antonio & Bonilla, Félix & Peña, Cristina. Functional heterogeneity of cancer-associated fibroblasts from human colon tumors shows specific prognostic gene expression signature.

https://hdl.handle.net/20.500.12080/39557
dc.contributor.author Herrera, Mercedes
dc.contributor.author Islam, Abul B M M K
dc.contributor.author Herrera, Alberto
dc.contributor.author Martín, Paloma
dc.contributor.author García, Vanesa
dc.contributor.author Silva, Javier
dc.contributor.author Garcia, Jose M
dc.contributor.author Salas, Clara
dc.contributor.author Casal, Ignacio
dc.contributor.author García de Herreros, Antonio
dc.contributor.author Bonilla, Félix
dc.contributor.author Peña, Cristina
dc.date.accessioned 2024-02-07T20:58:59Z
dc.date.available 2024-02-07T20:58:59Z
dc.date.created 2013-09
dc.identifier.uri https://hdl.handle.net/20.500.12080/39557
dc.description.abstract Purpose: Cancer-associated fibroblasts (CAF) actively participate in reciprocal communication with tumor cells and with other cell types in the microenvironment, contributing to a tumor-permissive neighborhood and promoting tumor progression. The aim of this study is the characterization of how CAFs from primary human colon tumors promote migration of colon cancer cells. Experimental design: Primary CAF cultures from 15 primary human colon tumors were established. Their enrichment in CAFs was evaluated by the expression of various epithelial and myofibroblast specific markers. Coculture assays of primary CAFs with different colon tumor cells were performed to evaluate promigratory CAF-derived effects on cancer cells. Gene expression profiles were developed to further investigate CAF characteristics. Results: Coculture assays showed significant differences in fibroblast-derived paracrine promigratory effects on cancer cells. Moreover, the association between CAFs' promigratory effects on cancer cells and classic fibroblast activation or stemness markers was observed. CAF gene expression profiles were analyzed by microarray to identify deregulated genes in different promigratory CAFs. The gene expression signature, derived from the most protumorogenic CAFs, was identified. Interestingly, this "CAF signature" showed a remarkable prognostic value for the clinical outcome of patients with colon cancer. Moreover, this prognostic value was validated in an independent series of 142 patients with colon cancer, by quantitative real-time PCR (qRT-PCR), with a set of four genes included in the "CAF signature." Conclusions: In summary, these studies show for the first time the heterogeneity of primary CAFs' effect on colon cancer cell migration. A CAF gene expression signature able to classify patients with colon cancer into high- and low-risk groups was identified. es_ES
dc.format application/pdf es_ES
dc.language eng es_ES
dc.publisher ACCR es_ES
dc.rights CC-BY es_ES
dc.rights.uri http://creativecommons.org/licenses/by/4.0/deed.es es_ES
dc.source Clinical Cancer Research es_ES
dc.title Functional heterogeneity of cancer-associated fibroblasts from human colon tumors shows specific prognostic gene expression signature es_ES
dc.type info:eu-repo/semantics/article es_ES
dc.rights.accessrights info:eu-repo/semantics/openAccess es_ES
dc.identifier.location N/A es_ES


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