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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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Summary of the suggested mechanism for the regulation of MMPs and TIMPs in the paracrine interplay between SCC-25 cells and fibroblasts. MMP-9 showed a tumor specific expression, regulated presumably by the fibronectin ITGA5B6 pathway. The ITGA5 was inducible in both SCC-25 and PDL fibroblasts in co-culture, but ITGB6 expression was tumor (SCC-25) specific. Based on a previous report [44], MMP-9 might be activated in interaction with CD-44, and according to our gelatinase assay results, it remains bound with the tumor cells (A). The results of this study suggest that MMP-2 is secreted in its pro- (inactive-) form by CAFs surrounding the tumor cells, and at a lower extent also by the tumor cells themselves. Activation of MMP-2 either requires MT1-MMP localized on the SCC-25 cancer cells [34], or integrins, where the involvement of αv integrins (ITGA5) is expected (A).MMPs-1, -3 and TIMPs-1, -3 are produced in the PDL fibroblasts, and their expression might be regulated by inflammatory cytokines, including IL1-β produced by SCC-25 cells. The gene expression of MMP-1, MMP-2, TIMP-1 and TIMP-3 was reduced by dexamethasone (DEX) (B).
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f0010: Summary of the suggested mechanism for the regulation of MMPs and TIMPs in the paracrine interplay between SCC-25 cells and fibroblasts. MMP-9 showed a tumor specific expression, regulated presumably by the fibronectin ITGA5B6 pathway. The ITGA5 was inducible in both SCC-25 and PDL fibroblasts in co-culture, but ITGB6 expression was tumor (SCC-25) specific. Based on a previous report [44], MMP-9 might be activated in interaction with CD-44, and according to our gelatinase assay results, it remains bound with the tumor cells (A). The results of this study suggest that MMP-2 is secreted in its pro- (inactive-) form by CAFs surrounding the tumor cells, and at a lower extent also by the tumor cells themselves. Activation of MMP-2 either requires MT1-MMP localized on the SCC-25 cancer cells [34], or integrins, where the involvement of αv integrins (ITGA5) is expected (A).MMPs-1, -3 and TIMPs-1, -3 are produced in the PDL fibroblasts, and their expression might be regulated by inflammatory cytokines, including IL1-β produced by SCC-25 cells. The gene expression of MMP-1, MMP-2, TIMP-1 and TIMP-3 was reduced by dexamethasone (DEX) (B).

Mentions: A continuous interaction between tumor cells and fibroblasts was hypothesized in the regulation of MMP and TIMP expression and activity. The expression of MMPs and TIMPs was expected in the PDL fibroblasts, whose regulation was hypothesized to occur via inflammatory cytokines, including IL1-β [32], produced by SCC-25 cells. In the regulation of MMP-9 gene expression the fibronectin–integrin αvβ6 (ITGA5B6) pathway was hypothesized. Another possible pathway, especially in regulation of TIMP expression, is the TGF-β1-pathway [31,32]; the expression of TGF-β1 was expected in the fibroblasts and in the tumor cells (Fig. 1).


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)

Summary of the suggested mechanism for the regulation of MMPs and TIMPs in the paracrine interplay between SCC-25 cells and fibroblasts. MMP-9 showed a tumor specific expression, regulated presumably by the fibronectin ITGA5B6 pathway. The ITGA5 was inducible in both SCC-25 and PDL fibroblasts in co-culture, but ITGB6 expression was tumor (SCC-25) specific. Based on a previous report [44], MMP-9 might be activated in interaction with CD-44, and according to our gelatinase assay results, it remains bound with the tumor cells (A). The results of this study suggest that MMP-2 is secreted in its pro- (inactive-) form by CAFs surrounding the tumor cells, and at a lower extent also by the tumor cells themselves. Activation of MMP-2 either requires MT1-MMP localized on the SCC-25 cancer cells [34], or integrins, where the involvement of αv integrins (ITGA5) is expected (A).MMPs-1, -3 and TIMPs-1, -3 are produced in the PDL fibroblasts, and their expression might be regulated by inflammatory cytokines, including IL1-β produced by SCC-25 cells. The gene expression of MMP-1, MMP-2, TIMP-1 and TIMP-3 was reduced by dexamethasone (DEX) (B).
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3378977&req=5

f0010: Summary of the suggested mechanism for the regulation of MMPs and TIMPs in the paracrine interplay between SCC-25 cells and fibroblasts. MMP-9 showed a tumor specific expression, regulated presumably by the fibronectin ITGA5B6 pathway. The ITGA5 was inducible in both SCC-25 and PDL fibroblasts in co-culture, but ITGB6 expression was tumor (SCC-25) specific. Based on a previous report [44], MMP-9 might be activated in interaction with CD-44, and according to our gelatinase assay results, it remains bound with the tumor cells (A). The results of this study suggest that MMP-2 is secreted in its pro- (inactive-) form by CAFs surrounding the tumor cells, and at a lower extent also by the tumor cells themselves. Activation of MMP-2 either requires MT1-MMP localized on the SCC-25 cancer cells [34], or integrins, where the involvement of αv integrins (ITGA5) is expected (A).MMPs-1, -3 and TIMPs-1, -3 are produced in the PDL fibroblasts, and their expression might be regulated by inflammatory cytokines, including IL1-β produced by SCC-25 cells. The gene expression of MMP-1, MMP-2, TIMP-1 and TIMP-3 was reduced by dexamethasone (DEX) (B).
Mentions: A continuous interaction between tumor cells and fibroblasts was hypothesized in the regulation of MMP and TIMP expression and activity. The expression of MMPs and TIMPs was expected in the PDL fibroblasts, whose regulation was hypothesized to occur via inflammatory cytokines, including IL1-β [32], produced by SCC-25 cells. In the regulation of MMP-9 gene expression the fibronectin–integrin αvβ6 (ITGA5B6) pathway was hypothesized. Another possible pathway, especially in regulation of TIMP expression, is the TGF-β1-pathway [31,32]; the expression of TGF-β1 was expected in the fibroblasts and in the tumor cells (Fig. 1).

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