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Tumor cell and carcinoma-associated fibroblast interaction regulates matrix metalloproteinases and their inhibitors in oral squamous cell carcinoma.

Fullár A, Kovalszky I, Bitsche M, Romani A, Schartinger VH, Sprinzl GM, Riechelmann H, Dudás J - Exp. Cell Res. (2012)

Bottom Line: In addition, these cells also cooperated in activation of MMP pro-enzymes.It is particularly interesting that the fibroblast-produced inactive MMP-2 has been activated by the tumor-cell-produced membrane-type 1 matrix metalloproteinase (MT1-MMP).The crosstalk between cancer- and the surrounding fibroblast stromal-cells is essential for the fine tuning of cancer cells invasivity.

View Article: PubMed Central - PubMed

Affiliation: 1st Department of Pathology and Experimental Cancer Research, Semmelweis University, Üllői út 26, 1085 Budapest, Hungary. fullarsz@gmail.com

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mRNA expression of ITGA5 (A), ITGB6 (B) and fibronectin (C), in PDL fibroblasts and SCC-25 cells in control and co-cultured conditions. *: p < 0.05; **: p < 0.01, ***: p < 0.001. Western blot of ITGA5 and loading control β-actin (D) in nuclear-free extracts of control (1) and co-cultured (2) fibroblasts, control (3) and co-cultured (4) SCC-25 cells. Confocal microscopy of EDA-fibronectin (red detected by Alexa fluor 647–conjugated anti-mouse IgG) in PDLs, bar: 100 μm.
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f0030: mRNA expression of ITGA5 (A), ITGB6 (B) and fibronectin (C), in PDL fibroblasts and SCC-25 cells in control and co-cultured conditions. *: p < 0.05; **: p < 0.01, ***: p < 0.001. Western blot of ITGA5 and loading control β-actin (D) in nuclear-free extracts of control (1) and co-cultured (2) fibroblasts, control (3) and co-cultured (4) SCC-25 cells. Confocal microscopy of EDA-fibronectin (red detected by Alexa fluor 647–conjugated anti-mouse IgG) in PDLs, bar: 100 μm.

Mentions: It was previously reported that fibronectin, via the αvβ6 integrin receptor (ITGA5B6) might upregulate MMP-9 gene expression [32]. Since IL-1β-treatment did not significantly contribute to MMP-9 gene expression in SCC-25 cells, it was investigated, if fibronectin, via ITGA5B6 receptor might have a contribution to MMP-9 regulation. Integrin αv (ITGA5) was constitutively expressed in both PDLs and SCC-25 cells (Fig. 5A). In co-culture, it was significantly upregulated in both of them (2.9 ± 1-times in fibroblasts and 2 ± 0.3-times in SCC-25 cells, using Mann–Whitney test) (Fig. 5A), which has been confirmed at the protein level as well (Fig. 5D). Integrin β6 (ITGB6) was expressed only in SCC-25 cells, and its gene expression remained unchanged in co-culture (p = 0.1, using Mann–Whitney test, Fig. 5B). In SCC-25 cells both αv and β6 integrins were present, their expression levels were comparable with the one of MMP-9 (Figs. 2F, 5A–B), and the SCC-25-specific expression of ITGB6 was also comparable with the SCC-25-specific expression of MMP-9.


Tumor cell and carcinoma-associated fibroblast interaction regulates matrix metalloproteinases and their inhibitors in oral squamous cell carcinoma.

Fullár A, Kovalszky I, Bitsche M, Romani A, Schartinger VH, Sprinzl GM, Riechelmann H, Dudás J - Exp. Cell Res. (2012)

mRNA expression of ITGA5 (A), ITGB6 (B) and fibronectin (C), in PDL fibroblasts and SCC-25 cells in control and co-cultured conditions. *: p < 0.05; **: p < 0.01, ***: p < 0.001. Western blot of ITGA5 and loading control β-actin (D) in nuclear-free extracts of control (1) and co-cultured (2) fibroblasts, control (3) and co-cultured (4) SCC-25 cells. Confocal microscopy of EDA-fibronectin (red detected by Alexa fluor 647–conjugated anti-mouse IgG) in PDLs, bar: 100 μm.
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Related In: Results  -  Collection

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f0030: mRNA expression of ITGA5 (A), ITGB6 (B) and fibronectin (C), in PDL fibroblasts and SCC-25 cells in control and co-cultured conditions. *: p < 0.05; **: p < 0.01, ***: p < 0.001. Western blot of ITGA5 and loading control β-actin (D) in nuclear-free extracts of control (1) and co-cultured (2) fibroblasts, control (3) and co-cultured (4) SCC-25 cells. Confocal microscopy of EDA-fibronectin (red detected by Alexa fluor 647–conjugated anti-mouse IgG) in PDLs, bar: 100 μm.
Mentions: It was previously reported that fibronectin, via the αvβ6 integrin receptor (ITGA5B6) might upregulate MMP-9 gene expression [32]. Since IL-1β-treatment did not significantly contribute to MMP-9 gene expression in SCC-25 cells, it was investigated, if fibronectin, via ITGA5B6 receptor might have a contribution to MMP-9 regulation. Integrin αv (ITGA5) was constitutively expressed in both PDLs and SCC-25 cells (Fig. 5A). In co-culture, it was significantly upregulated in both of them (2.9 ± 1-times in fibroblasts and 2 ± 0.3-times in SCC-25 cells, using Mann–Whitney test) (Fig. 5A), which has been confirmed at the protein level as well (Fig. 5D). Integrin β6 (ITGB6) was expressed only in SCC-25 cells, and its gene expression remained unchanged in co-culture (p = 0.1, using Mann–Whitney test, Fig. 5B). In SCC-25 cells both αv and β6 integrins were present, their expression levels were comparable with the one of MMP-9 (Figs. 2F, 5A–B), and the SCC-25-specific expression of ITGB6 was also comparable with the SCC-25-specific expression of MMP-9.

Bottom Line: In addition, these cells also cooperated in activation of MMP pro-enzymes.It is particularly interesting that the fibroblast-produced inactive MMP-2 has been activated by the tumor-cell-produced membrane-type 1 matrix metalloproteinase (MT1-MMP).The crosstalk between cancer- and the surrounding fibroblast stromal-cells is essential for the fine tuning of cancer cells invasivity.

View Article: PubMed Central - PubMed

Affiliation: 1st Department of Pathology and Experimental Cancer Research, Semmelweis University, Üllői út 26, 1085 Budapest, Hungary. fullarsz@gmail.com

Show MeSH
Related in: MedlinePlus