2024-03-28T19:08:24Zhttp://digital.csic.es/dspace-oai/requestoai:digital.csic.es:10261/2108232020-11-12T13:25:48Zcom_10261_86com_10261_1col_10261_339
Proteome profiling of cancer-associated fibroblasts identifies novel proinflammatory signatures and prognostic markers for colorectal cancer
Torres, Sofía
Bartolomé, Rubén Álvaro
Mendes, Marta
Barderas, Rodrigo
Fernandez-Aceñero, M. Jesús
Peláez-García, Alberto
Peña, Cristina
López-Lucendo, María F.
Villar-Vázquez, Roi
García de Herreros, Antonio
Bonilla, Félix
Casal, J. Ignacio
Asociación Española Contra el Cáncer
Ministerio de Ciencia e Innovación (España)
Comunidad de Madrid
Torres, Sofía [0000-0002-9007-8105]
Bartolomé, Rubén Álvaro [0000-0002-3292-1491]
Mendes, Marta [0000-0002-3528-7123]
Barderas, Rodrigo [0000-0003-3539-7469]
Fernandez-Aceñero, M. Jesús [0000-0002-2439-3553]
Villar-Vázquez, Roi [0000-0001-8314-7451]
García de Herreros, Antonio [0000-0001-5270-0808]
Casal, J. Ignacio [0000-0003-1085-2840]
Growth-factor-beta
Gene-expression
Colon cancer
Mesenchymal transition
Tumor microenvironment
Stromal myofibroblasts
Metastasis
Invasion
Cells
Mice
15 p.-5 fig.-1 tab.
PURPOSE:Cancer-associated fibroblasts (CAF) are essential components of the stroma that play a critical role in cancer progression. This study aimed to identify novel CAFs markers that might contribute to the invasion and the prognosis of colorectal cancer.
EXPERIMENTAL DESIGN:The azoxymethane/dextran sodium sulfate mouse model of sporadic colon cancer represents an adequate source for the isolation of CAFs and normal fibroblasts. By using the explants technique, we purified CAFs and normal fibroblasts from colon tissues. Whole-cell extracts and supernatants were subjected to in-depth quantitative proteomic analysis by tandem mass spectrometry. Further validations of upregulated proteins in CAFs were carried out by chemokine microarray and immunohistochemical analyses of mouse and human tissues.
RESULTS:Using a fold-change of 1.4 or more, we found 132 and 125 differentially expressed proteins in whole-cell extracts and supernatants, respectively. We found CAFs-associated proinflammatory and desmoplastic signatures. The proinflammatory signature was composed of several cytokines. Among them, CCL2 and CCL8 caused an increase in migration and invasion of colorectal cancer KM12 cells. The desmoplastic signature was composed of 30 secreted proteins. In mouse and human samples, expression of LTBP2, CDH11, OLFML3, and, particularly, FSTL1 was significantly increased in the tumoral stroma, without significant expression in the cancer epithelial cells. The combination of CALU and CDH11 stromal expression showed a significant association with disease-free survival and poor prognosis.
CONCLUSION:We have identified LTBP2, CDH11, OLFML3, and FSTL1 as selective biomarkers of cancer stroma, and CALU and CDH11 as candidate stromal biomarkers of prognostic significance in colon cancer.
2020-05-08T12:00:37Z
2020-05-08T12:00:37Z
2013-11-01
artículo
Clin Cancer Res 19 (21) 6006-19 (2013)
1078-0432
http://hdl.handle.net/10261/210823
10.1158/1078-0432.CCR-13-1130
1557-3265
http://dx.doi.org/10.13039/501100004837
http://dx.doi.org/10.13039/100012818
eng
https://doi.org/10.1158/1078-0432.CCR-13-1130
Sí
closedAccess
American Association for Cancer Research