Abstract
Background
Concerted alterations between stromal fibroblasts and neoplastic cells underline the carcinogenic process. Activation of alpha-smooth muscle actin (SMA) expression, a cytoskeleton protein normally expressed only in myoepithelial cells, is considered a landmark for the activation of stromal fibroblasts with little however being known regarding the mechanism governing the expression of SMA in the stroma.
Methods
We have evaluated by immunohistochemistry the expression of SMA in the stroma of oral malignant and pre-malignant lesions, in association with the expression of p53 and p21 tumor suppressors that were shown previously to be deregulated and/or mutated in stromal fibroblasts of various cancers. The effects of p21 knockdown in SMA expression and cell migration and the mRNA levels of endogenous p21 in fibroblasts co-cultured with cancer cells were also assessed.
Results
We found that both p21 and SMA expression was elevated in the stroma, but not the epithelium, of malignant as compared to pre-malignant lesions. We also noted that the expression of both was positively correlated, implying that SMA expression may be regulated by p21. Consistently with this notion we found that siRNA-mediated p21 suppression resulted in the reduction of SMA levels and also inhibited cell migration.
Conclusion
Our results show that p21 deregulation is associated with the activation of stromal fibroblasts of oral cancers by a mechanism that involves the stimulation of SMA expression.
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Acknowledgements
This study was supported by grants from ‘KESY’, Ministry of Health, Greece and ‘Kapodistrias’, ELKE, University of Athens.
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This paper is a reprint from ‘p21/waf1 and smooth-muscle actin α expression in stromal fibroblasts of oral cancers, Ioulia Chatzistamou, Nikolina Dioufa, George Trimis, Alexandra Sklavounou, Christos Kittas, Hippokratis Kiaris and Athanasios G. Papavassiliou’ originally published in Analytical Cellular Pathology/Cellular Oncology, Volume 33, number 1, 2010, pp. 19-26, IOS Press.
An erratum to this article can be found at http://dx.doi.org/10.1007/s13402-011-0063-3
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Chatzistamou, I., Dioufa, N., Trimis, G. et al. p21/waf1 and smooth-muscle actin α expression in stromal fibroblasts of oral cancers. Cell Oncol. 34, 483–488 (2011). https://doi.org/10.1007/s13402-011-0044-6
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DOI: https://doi.org/10.1007/s13402-011-0044-6