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

Astrid De Boeck UGent, An Hendrix UGent, Dawn Maynard, Mieke Van Bockstal UGent, Annick Daniëls, Patrick Pauwels UGent, Christian Gespach, Marc Bracke UGent and Olivier De Wever UGent (2013) PROTEOMICS. 13(2). p.379-388
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.
Please use this url to cite or link to this publication:
author
organization
year
type
journalArticle (original)
publication status
published
subject
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
journal title
PROTEOMICS
Proteomics
volume
13
issue
2
issue title
Focus on bioinformatics in proteomics
pages
379 - 388
Web of Science type
Article
Web of Science id
000313981800018
JCR category
BIOCHEMICAL RESEARCH METHODS
JCR impact factor
3.973 (2013)
JCR rank
14/78 (2013)
JCR quartile
1 (2013)
ISSN
1615-9853
DOI
10.1002/pmic.201200179
language
English
UGent publication?
yes
classification
A1
copyright statement
I have transferred the copyright for this publication to the publisher
id
3123909
handle
http://hdl.handle.net/1854/LU-3123909
date created
2013-02-07 11:29:21
date last changed
2016-12-19 15:39:32
@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},
}

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.