Title
Differential secretome analysis of cancer-associated fibroblasts and bone marrow-derived precursors to identify microenvironmental regulators of colon cancer progression Differential secretome analysis of cancer-associated fibroblasts and bone marrow-derived precursors to identify microenvironmental regulators of colon cancer progression
Author
Faculty/Department
Faculty of Medicine and Health Sciences
Publication type
article
Publication
Weinheim ,
Subject
Chemistry
Biology
Source (journal)
Proteomics. - Weinheim
Volume/pages
13(2013) :2 , p. 379-388
ISSN
1615-9853
ISI
000313981800018
Carrier
E
Target language
English (eng)
Full text (Publishers DOI)
Affiliation
University of Antwerp
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 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.
E-info
https://repository.uantwerpen.be/docman/iruaauth/35b50f/3955052.pdf
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