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Differential secretome analysis of cancer‐associated fibroblasts and bone marrow‐derived precursors to identify microenvironmental regulators of colon cancer progression
Author(s) -
De Boeck Astrid,
Hendrix An,
Maynard Dawn,
Van Bockstal Mieke,
Daniëls Annick,
Pauwels Patrick,
Gespach Christian,
Bracke Marc,
De Wever Olivier
Publication year - 2013
Publication title -
proteomics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.26
H-Index - 167
eISSN - 1615-9861
pISSN - 1615-9853
DOI - 10.1002/pmic.201200179
Subject(s) - stromal cell , cancer research , biology , bone marrow , cancer cell , cancer , cancer associated fibroblasts , mesenchymal stem cell , tumor microenvironment , pathology , microbiology and biotechnology , immunology , medicine , genetics , tumor cells
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 CAF s. 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 R antes, 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.