OP093: Expression of αvβ3-integrins in oral squamous cell cancer and as a target of molecular imaging in an orthotopic mouse model

2013 
Purpose Integrins are adhesion molecules and play a role in many cellular processes, e. g. angiogenesis, tumor development and metastasis. Monoclonal antibodies directed to α v β 3-integrins are tested in clinical studies for the treatment of advances malignant melanoma and could be an option for the treatment of oral cancer. Material and methods Biopsies were taken from 83 histological proven oral squamous cell cancers, the mRNA was isolated and the gene expression was measured with “whole genome microarrays“. Expression patterns were compared to biopsies from the oral mucosa of healthy volunteers. The expression of the α v- and β 3-subunit was analyzed. In an orthotopic xenograft mouse model of oral cancer tumors were induced by sonographic controlled injection of 1 × 10 6 SCC-9 cells, a human squamous cell cancer cell line, in the floor of the mouth in Fox-n1 nude mice. Tumors or recurrent tumors ( n  = 10) were visualized in a fluorescence-chamber (Berthold NightOWL) after the application of “Integrisense” (visen medical) via the tail vein. Integrisense binds to α v β 3-integrins and is labeled with a fluorochrome. Results The microarray-analysis showed an upregulation of the α v- and β 3-subunit in 40% of the tumor samples. Even though the cell line SCC-9 showed in vitro no upregulation of α v β 3-integrins, it could be shown that Integrisense binds to the tumors that were induced in vivo in the mouse model. The best signal-to-noise-ratio was measured one day after the application. The intensity of the fluorescence-signal was between 245 nm and 510 nm counts per second. Conclusion α v β 3-Integrins are a possible target for the visualisation of the tumor with fluorochrome-labeled probes and are a possible therapeutic target for selected oral squamous cell carcinomas.
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