科研之友
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摘要
BACKGROUND: Integrins initiate signalling in response to the extracellular matrix (ECM), which is important in wound healing and cancer. Previous studies have shown that over-expression of the alpha v beta 6 integrin in oral squamous cell carcinoma (OSCC) cells results in enhanced motility and expression of matrix-degrading proteases, and the aim of this study was to investigate whether this is also the case for the alpha 9 beta 1 integrin.
METHODS: H357 OSCCcells were transfected with the alpha 9 integrin subunit and proliferation, adhesion and migration assays were performed on these along with null vector control and wild-type cells. The effect of ligand engagement on matrix metalloproteinase expression and the plasminogen activator system was measured using ELISA and chromogenic assays. Expression of alpha 9 integrin was examined in oral squamous cell carcinoma tissue by immunohistochemistry.
RESULTS: Functionally active alpha 9 integrin mediated specific upregulation of adhesion and migration towards the TNfn3RAA fragment of tenascin-C but reduced proliferation. Migration towards collagen I was also enhanced in transfected cells. Matrix metalloproteinase-2 and metalloproteinase-9 expression was increased upon TNfn3RAA ligand engagement. Cell surface plasmin generation was also enhanced in alpha 9-expressing cells and was the result of enhanced expression of urokinase receptor. In normal oral mucosa, alpha 9 integrin expression was restricted to the suprabasal and prickle cell layers, and expression was heterogeneous in tumours but present in islands infiltrating connective tissue particularly in moderately and well-differentiated lesions.
CONCLUSIONS: The alpha 9 beta 1 integrin may play a key role in modulation of tumour behaviour including enhanced cell migration and expression of matrix-degrading proteases. J Oral Pathol Med (2011) 40: 755-761
- 出版日期2011-11
