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Differential secretome analysis of cancer-associated fibroblasts and bone marrow-derived precursors to identify microenvironmental regulators of colon cancer progression

(2013) PROTEOMICS. 13(2). p.379-388
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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 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.
Keywords
Cell Biology, Cancer-associated fibroblasts, Colon cancer, Mesenchymal stem cells, MS, Secretome, MESENCHYMAL STROMAL CELLS, PROMOTE TUMOR-GROWTH, PROTEOMIC ANALYSIS, MASS-SPECTROMETRY, GENE-EXPRESSION, BREAST-CANCER, STEM-CELLS, CONDITIONED MEDIA, TISSUE, MYOFIBROBLASTS

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Citation

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Chicago
De Boeck, Astrid, An Hendrix, Dawn Maynard, Mieke Van Bockstal, Annick Daniëls, Patrick Pauwels, Christian Gespach, Marc Bracke, and Olivier De Wever. 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.
APA
De Boeck, Astrid, Hendrix, A., Maynard, D., Van Bockstal, M., Daniëls, A., Pauwels, P., Gespach, C., et al. (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.
Vancouver
1.
De Boeck A, Hendrix A, Maynard D, Van Bockstal M, Daniëls A, Pauwels P, et al. Differential secretome analysis of cancer-associated fibroblasts and bone marrow-derived precursors to identify microenvironmental regulators of colon cancer progression. PROTEOMICS. 2013;13(2):379–88.
MLA
De Boeck, Astrid, An Hendrix, Dawn Maynard, et al. “Differential Secretome Analysis of Cancer-associated Fibroblasts and Bone Marrow-derived Precursors to Identify Microenvironmental Regulators of Colon Cancer Progression.” PROTEOMICS 13.2 (2013): 379–388. Print.
@article{3123909,
  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.},
  author       = {De Boeck, Astrid and Hendrix, An and Maynard, Dawn and Van Bockstal, Mieke and Dani{\"e}ls, Annick and Pauwels, Patrick and Gespach, Christian and Bracke, Marc and De Wever, Olivier},
  issn         = {1615-9853},
  journal      = {PROTEOMICS},
  keyword      = {Cell Biology,Cancer-associated fibroblasts,Colon cancer,Mesenchymal stem cells,MS,Secretome,MESENCHYMAL STROMAL CELLS,PROMOTE TUMOR-GROWTH,PROTEOMIC ANALYSIS,MASS-SPECTROMETRY,GENE-EXPRESSION,BREAST-CANCER,STEM-CELLS,CONDITIONED MEDIA,TISSUE,MYOFIBROBLASTS},
  language     = {eng},
  number       = {2},
  pages        = {379--388},
  title        = {Differential secretome analysis of cancer-associated fibroblasts and bone marrow-derived precursors to identify microenvironmental regulators of colon cancer progression},
  url          = {http://dx.doi.org/10.1002/pmic.201200179},
  volume       = {13},
  year         = {2013},
}

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