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Differential regulation of extracellular matrix protein expression in carcinoma-associated fibroblasts by TGF-β1 regulates cancer cell spreading but not adhesion

Mieke Van Bockstal (UGent) , Kathleen Lambein (UGent) , Mireille Van Gele (UGent) , Elly De Vlieghere (UGent) , RIDHA LIMAME (UGent) , Geert Braems (UGent) , Rudy Van den Broecke (UGent) , Veronique Cocquyt (UGent) , Hannelore Denys (UGent) , Marc Bracke (UGent) , et al.
(2014) ONCOSCIENCE. 1(10). p.634-648
Author
Organization
Abstract
Cancer progression is characterized by a complex reciprocity between neoplastic epithelium and adjacent stromal cells. In ductal carcinoma in situ (DCIS) of the breast, both reduced stromal decorin expression and myxoid stroma are correlated with increased recurrence risk. In this study, we aimed to investigate paracrine regulation of expression of decorin and related extracellular matrix (ECM) proteins in cancerassociated fibroblasts (CAFs). Transforming growth factor-β1 (TGF-β1) was identified as a competent ECM modulator, as it reduced decorin and strongly enhanced versican, biglycan and type I collagen expression. Similar but less pronounced effects were observed when fibroblasts were treated with basic fibroblast growth factor (bFGF). Despite this concerted ECM modulation, TGF-β1 and bFGF differentially regulated alpha-smooth muscle actin (α-SMA) expression, which is often proposed as a CAFmarker. Cancer cell-derived secretomes induced versican and biglycan expression in fibroblasts. Immunohistochemistry on twenty DCIS specimens showed a trend toward periductal versican overexpression in DCIS with myxoid stroma. Cancer cell adhesion was inhibited by decorin, but not by CAF-derived matrices. Cancer cells presented significantly enhanced spreading when seeded on matrices derived from TGF-β1-treated CAF. Altogether these data indicate that preinvasive cancerous lesions might modulate the composition of surrounding stroma through TGF-β1 release to obtain an invasion-permissive microenvironment.
Keywords
Stromal protein expression, Cancer-associated fibroblasts, TGF-β1, Decorin, Versican

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MLA
Van Bockstal, Mieke, Kathleen Lambein, Mireille Van Gele, et al. “Differential Regulation of Extracellular Matrix Protein Expression in Carcinoma-associated Fibroblasts by TGF-β1 Regulates Cancer Cell Spreading but Not Adhesion.” ONCOSCIENCE 1.10 (2014): 634–648. Print.
APA
Van Bockstal, M., Lambein, K., Van Gele, M., De Vlieghere, E., LIMAME, R., Braems, G., Van den Broecke, R., et al. (2014). Differential regulation of extracellular matrix protein expression in carcinoma-associated fibroblasts by TGF-β1 regulates cancer cell spreading but not adhesion. ONCOSCIENCE, 1(10), 634–648.
Chicago author-date
Van Bockstal, Mieke, Kathleen Lambein, Mireille Van Gele, Elly De Vlieghere, RIDHA LIMAME, Geert Braems, Rudy Van den Broecke, et al. 2014. “Differential Regulation of Extracellular Matrix Protein Expression in Carcinoma-associated Fibroblasts by TGF-β1 Regulates Cancer Cell Spreading but Not Adhesion.” Oncoscience 1 (10): 634–648.
Chicago author-date (all authors)
Van Bockstal, Mieke, Kathleen Lambein, Mireille Van Gele, Elly De Vlieghere, RIDHA LIMAME, Geert Braems, Rudy Van den Broecke, Veronique Cocquyt, Hannelore Denys, Marc Bracke, Louis Libbrecht, and Olivier De Wever. 2014. “Differential Regulation of Extracellular Matrix Protein Expression in Carcinoma-associated Fibroblasts by TGF-β1 Regulates Cancer Cell Spreading but Not Adhesion.” Oncoscience 1 (10): 634–648.
Vancouver
1.
Van Bockstal M, Lambein K, Van Gele M, De Vlieghere E, LIMAME R, Braems G, et al. Differential regulation of extracellular matrix protein expression in carcinoma-associated fibroblasts by TGF-β1 regulates cancer cell spreading but not adhesion. ONCOSCIENCE. 2014;1(10):634–48.
IEEE
[1]
M. Van Bockstal et al., “Differential regulation of extracellular matrix protein expression in carcinoma-associated fibroblasts by TGF-β1 regulates cancer cell spreading but not adhesion,” ONCOSCIENCE, vol. 1, no. 10, pp. 634–648, 2014.
@article{5863666,
  abstract     = {Cancer progression is characterized by a complex reciprocity between neoplastic epithelium and adjacent stromal cells. In ductal carcinoma in situ (DCIS) of the breast, both reduced stromal decorin expression and myxoid stroma are correlated with increased recurrence risk. In this study, we aimed to investigate paracrine regulation of expression of decorin and related extracellular matrix (ECM) proteins in cancerassociated fibroblasts (CAFs). Transforming growth factor-β1 (TGF-β1) was identified as a competent ECM modulator, as it reduced decorin and strongly enhanced versican, biglycan and type I collagen expression. Similar but less pronounced effects were observed when fibroblasts were treated with basic fibroblast growth factor (bFGF). Despite this concerted ECM modulation, TGF-β1 and bFGF differentially regulated alpha-smooth muscle actin (α-SMA) expression, which is often proposed as a CAFmarker. Cancer cell-derived secretomes induced versican and biglycan expression in fibroblasts. Immunohistochemistry on twenty DCIS specimens showed a trend toward periductal versican overexpression in DCIS with myxoid stroma. Cancer cell adhesion was inhibited by decorin, but not by CAF-derived matrices. Cancer cells presented significantly enhanced spreading when seeded on matrices derived from TGF-β1-treated CAF. Altogether these data indicate that preinvasive cancerous lesions might modulate the composition of surrounding stroma through TGF-β1 release to obtain an invasion-permissive microenvironment.},
  author       = {Van Bockstal, Mieke and Lambein, Kathleen and Van Gele, Mireille and De Vlieghere, Elly and LIMAME, RIDHA and Braems, Geert and Van den Broecke, Rudy and Cocquyt, Veronique and Denys, Hannelore and Bracke, Marc and Libbrecht, Louis and De Wever, Olivier},
  issn         = {2331-4737},
  journal      = {ONCOSCIENCE},
  keywords     = {Stromal protein expression,Cancer-associated fibroblasts,TGF-β1,Decorin,Versican},
  language     = {eng},
  number       = {10},
  pages        = {634--648},
  title        = {Differential regulation of extracellular matrix protein expression in carcinoma-associated fibroblasts by TGF-β1 regulates cancer cell spreading but not adhesion},
  url          = {http://www.impactjournals.com/oncoscience/index.php?abs=87},
  volume       = {1},
  year         = {2014},
}