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Title
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Differential secretome analysis of cancer-associated fibroblasts and bone marrow-derived precursors to identify microenvironmental regulators of colon cancer progression
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Author
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Abstract
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| 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 a-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-beta 1 (TGF-beta 1) is a crucial inducer of a-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-beta 1 on the secretion of proteins by bone marrow-derived MSC in comparison with the protein secretion profile of CAF. TGF-beta 1 induced de novo secretion of 84 proteins in MSC, of which 16 proteins, including stromal-derived factor-1a 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. |
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Language
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English
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Source (journal)
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Proteomics. - Weinheim
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Publication
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Weinheim
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2013
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ISSN
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1615-9853
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DOI
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10.1002/PMIC.201200179
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Volume/pages
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13
:2
(2013)
, p. 379-388
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ISI
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000313981800018
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Full text (Publisher's DOI)
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Full text (publisher's version - intranet only)
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