title: Differential secretome analysis of cancer-associated fibroblasts and bone marrow-derived precursors to identify microenvironmental regulators of colon cancer progression.
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.
authors.affiliation: Laboratory of Experimental Cancer Research, Department of Radiation Oncology and Experimental Cancer Research, Bethesda, MD, USA.
authors.forename: Astrid
authors.initials: A
authors.lastname: De Boeck
authors.forename: An
authors.initials: A
authors.lastname: Hendrix
authors.forename: Dawn
authors.initials: D
authors.lastname: Maynard
authors.forename: Mieke
authors.initials: M
authors.lastname: Van Bockstal
authors.forename: Annick
authors.initials: A
authors.lastname: Daniëls
authors.forename: Patrick
authors.initials: P
authors.lastname: Pauwels
authors.forename: Christian
authors.initials: C
authors.lastname: Gespach
authors.forename: Marc
authors.initials: M
authors.lastname: Bracke
authors.forename: Olivier
authors.initials: O
authors.lastname: De Wever
mesh_terms: D014408:Biomarkers, Tumor / Q000378:metabolism*; D001854:Bone Marrow Cells / Q000166:cytology; D003110:Colonic Neoplasms / Q000737:chemistry / Q000378:metabolism* / Q000473:pathology*; D018450:Disease Progression; D004797:Enzyme-Linked Immunosorbent Assay; D005347:Fibroblasts / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D007150:Immunohistochemistry; D059630:Mesenchymal Stem Cells; D009363:Neoplasm Proteins / Q000032:analysis / Q000378:metabolism*; D010641:Phenotype; D015203:Reproducibility of Results; D015398:Signal Transduction; D059016:Tumor Microenvironment
chemical_list: D014408:Biomarkers, Tumor; D009363:Neoplasm Proteins