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B. Hayek, M. Barry, A. Lacy-Hulbert, R. O. Hynes, B. Esmaeli, J. McCarty; A Novel Mouse Model to Study the Pathogenesis of Eyelid Squamous Cell Carcinoma. Invest. Ophthalmol. Vis. Sci. 2007;48(13):3992.
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Genetic alterations in cell adhesion and signaling that may be involved in the development of epithelial cancers are not well-elucidated. We herein investigate the functional contribution of alpha v (αv) integrin in regulating growth of the mouse eyelid epithelium and describe a mouse model for eyelid squamous cell carcinoma based on molecular dysregulation of the αv integrin molecule.
A conditional αv allele, αv flox, was selectively ablated in epithelial cells of the developing mouse eye using Cre transgenes. Genetic ablation of the αv gene was confirmed by genomic PCR to monitor recombination of the αv flox allele. Immunohistochemical staining using antibodies directed against αv integrin protein was done to analyze αv expression in basal epithelial cells of the conjunctiva and eyelid of the developing mouse. We analyzed cohorts of control and mutant mice to determine how loss of αv integrin allele and resultant loss of αv expression may influence basal epithelial cell development and neoplasia.
All mutant mice developed bilateral eyelid tumors. The mutant mice were viable and fertile. The eyelid tumors were grossly obvious by one year of age, but could be microscopically detected as early as the third post-natal month. The eyelid tumors were well-differentiated but had the ability to invade into the periocular soft tissues. On histopathologic evaluation, the eyelid tumors were similar to human squamous cell carcinoma. We detected significant Cre-mediated deletion of the αv flox gene in the post-natal eye but not in other peripheral tissues of the mutant mice. We detected Cre activity in the embryonic and neonatal eye of the R26R-loxSTOPlox:lacZ reporter strain. Av integrin was highly expressed in basal epithelial cells in the conjunctiva and eyelid of the non-mutant mice. However, the mutant mice lacked αv expression in the conjunctival and eyelid epithelial cells.
Cre-mediated ablation of αv integrin leads to the formation of squamous cell carcinoma of the eyelid and conjunctiva in mice. This suggests that αv integrin may be a critical regulator of epithelial cell growth and that loss of αv integrin may lead to neoplastic overgrowth of conjunctival and eyelid epithelial cells.
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