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Published on: October 20, 2019
Analysis of αv integrin protein expression in human eyelid and periorbital squamous cell carcinomas
Adam Hsu1, Bita Esmaeli, Brent Hayek
1Section of Ophthalmology, Department of Head and Neck Surgery, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Background:
Alpha v integrins are receptors for many extracellular matrix (ECM) protein ligands, including latent transforming growth factor betas (TGFβs). Various studies in mice have shown that ablation of genes encoding αv integrin or TGFβ signaling pathway components leads to spontaneous squamous cell carcinomas (SCCs) in the conjunctiva and periocular skin. Here, we have analyzed patterns of αv integrin protein expression and TGFβ signaling in human eyelid and periorbital SCC samples.
Methods:
An anti-αv integrin antibody was used to immunostain 19 eyelid and periorbital SCC samples. Additionally, tissue lysates from resected normal eyelid and SCC samples were analyzed by immunoblotting for αv integrin protein. Tumor sections were also immunostained with an antibody directed against Smad2, an intracellular signaling protein that is phosphorylated by TGFβ receptors.
Results:
Alpha v integrin protein was highly expressed in the invasive and less-differentiated components of human SCCs. Lower levels of αv integrin protein were detected in more differentiated components of tumors, as well as in SCC in situ. Patterns of phosphorylated Smad2 immunoreactivity correlated with levels αv integrin expression.
Conclusions:
Alpha v integrin was expressed at robust levels in tumor cells representing less differentiated, more invasive components of SCC; by contrast, well-differentiated cells as well as SCC in situ expressed low levels of αv integrin protein.
Insights
Alpha v integrin is highly expressed in invasive squamous cell carcinoma (SCC) cells, indicating a role in tumor progression. Lower expression is seen in less aggressive SCC, suggesting potential therapeutic targets.
Area of Science:
- Oncology
- Cell Biology
- Dermatology
Background:
- Alpha v integrins bind extracellular matrix proteins like transforming growth factor betas (TGFβs).
- Gene studies in mice link alpha v integrin or TGFβ pathway disruption to conjunctival and periocular squamous cell carcinomas (SCCs).
Purpose of the Study:
- To investigate alpha v integrin protein expression and TGFβ signaling in human eyelid and periorbital SCCs.
Main Methods:
- Immunostaining of 19 human eyelid and periorbital SCC samples for alpha v integrin.
- Immunoblotting of tissue lysates for alpha v integrin protein.
- Immunostaining for phosphorylated Smad2, a TGFβ signaling indicator.
Main Results:
- Alpha v integrin protein showed high expression in invasive, less-differentiated SCC components.
- Lower alpha v integrin levels were observed in well-differentiated SCC and SCC in situ.
- Phosphorylated Smad2 patterns correlated with alpha v integrin expression levels.
Conclusions:
- Robust alpha v integrin expression in less-differentiated, invasive SCC cells.
- Low alpha v integrin expression in well-differentiated SCC and SCC in situ.
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