Differential secretome analysis of cancer-associated fibroblasts and bone marrow-derived precursors to identify microenvironmental regulators of colon cancer progression.
(2013) Proteomics — Vol. 13, n° 2, p. 379-388 (2013)
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- Abstract
- The identification of cancer-associated fibroblast (CAF)-derived proteins that mediate interactions between the tumor stroma and cancer cells is a crucial step toward the discovery of new molecular targets for therapy or molecular signatures that improve tumor classification and predict clinical outcome. CAF are α-smooth muscle actin positive, representing a myofibroblast phenotype that may differentiate from multiple precursor cells, including bone marrow-derived mesenchymal stem cells (MSC). Transforming growth factor-β1 (TGF-β1) is a crucial inducer of α-smooth muscle actin positive CAFs. In this study, we aimed to identify CAF-derived regulators of colon cancer progression by performing a high-throughput differential secretome profiling between CAF compared to noncancer-activated bone marrow-derived MSC. In addition, we explored the effect of TGF-β1 on the secretion of proteins by bone marrow-derived MSC in comparison with the protein secretion profile of CAF. TGF-β1 induced de novo secretion of 84 proteins in MSC, of which 16 proteins, including stromal-derived factor-1α and Rantes, were also present in CAF secretome. Immunohistochemistry further validated the expression of selected candidates such as tenascin C, fibronectin ED-A domain and stromal-derived factor-1 in clinical colon cancer specimens. In conclusion, this differential secretome approach enabled us to identify a series of candidate biomarkers for colon cancer that are associated with a CAF-specific phenotype.
- Affiliations
Ghent University Hospital Department of Pathology
Citations
De Boeck, A., Hendrix, A., Maynard, D., Van Bockstal, M., Daniëls, A., Pauwels, P., Gespach, C., Bracke, M., & De Wever, O. (2013). Differential secretome analysis of cancer-associated fibroblasts and bone marrow-derived precursors to identify microenvironmental regulators of colon cancer progression. Proteomics, 13(2), 379-388. https://doi.org/10.1002/pmic.201200179 (Original work published 2013)