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A. Y. Hsu, B. Esmaeli, B. Hayek, A. Lazar, A. El-Naggar, J. McCarty; Analysis of v Integrin Expression in Human Conjunctiva, Eyelid, and Head and Neck Squamous Cell Carcinoma. Invest. Ophthalmol. Vis. Sci. 2008;49(13):5015.
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Integrins are cell adhesion molecules that play a role in cell proliferation, differentiation, and carcinogenesis. Our group has demonstrated that conditional deletion of αv integrin using Cre/lox technology leads to spontaneous development of conjunctival and eyelid squamous cell carcinoma (SCC) in mice. The goal of the current study was to investigate the expression of αv integrin in human conjunctival, eyelid, and head and neck (HN) SCC.
Nine formalin-fixed, paraffin-embedded human eyelid and palpebral conjunctival and nine head and neck SCC specimens were obtained from the Pathology Department at M. D. Anderson Cancer Center. Standard antigen retrieval and immunohistochemical staining (IHC) were performed. The IHC stain intensity was graded (from 0 to 3+) by two independent observers. Western blot analysis was done using total protein lysates from three human HN SCC cell lines; a wild-type human keratinocyte cell line served as the control.
Consistent with observations in our mouse model, αv integrin was highly expressed in the basal epithelial layer of conjunctiva and skin, hair follicles, sweat glands, and endothelium of blood vessels in the human samples. There was a consistent pattern of the most intense IHC staining (3+) in the peripheral/basal layer of SCC nests with lack of staining of the more well- differentiated cells in the center of the SCC nests seen in five specimens. Strong (2-3+) staining for αv was also seen in the infiltrative poorly differentiated tumor cells in two specimens, and in tumor cells infiltrating peripheral nerves in one. Western blot analysis of three human SCC cell lines with anti-αv antibody demonstrated the presence of αv at a similar level to control (wild-type human keratinocytes).
Down regulation of αv integrin was observed in the well-differentiated components of SCC in both ocular and non-ocular human samples. However, the more poorly differentiated and more invasive components expressed higher levels of αv integrin. Reduced αv integrin expression may play a role during human SCC initiation, but its expression may be upregulated as cancer cells progress to a more malignant phenotype. The αv integrin conditional knockout mouse model of conjunctival/eyelid SCC can serve as an interesting model for studying the role of integrins in human SCC and for development of potential novel treatment strategies for this common epithelial cancer.
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