Blood group antigens and integrins as biomarkers in head and neck cancer: Is aberrant tyrosine phosphorylation the cause of altered α6β4 integrin expression?
✍ Scribed by Dr. Thomas E. Carey; Thankam S. Nair; Catherine Chern; Monica Liebert; H. Barton Grossman; Gregory T. Wolf; Carter Van Waes
- Publisher
- John Wiley and Sons
- Year
- 1993
- Tongue
- English
- Weight
- 878 KB
- Volume
- 53
- Category
- Article
- ISSN
- 0730-2312
No coin nor oath required. For personal study only.
✦ Synopsis
Head and neck cancer is a capricious disease that varies greatly in its clinical behavior. The development of biomarkers that can distinguish between biologically aggressive and indolent tumors has been a long term goal of our laboratories. Predictive markers applicable to biopsy specimens should facilitate clinical management through early identification of patients at greatest risk for early relapse or metastatic spread. Two prominent cell surface markers that we identified by raising monoclonal antibodies to squamous cell carcinomas are blood group antigens and the A9 anti-genlcr6P4 integrin. Both of these markers are abnormally displayed in squamous cancers of the head and neck and serve as indicators of early relapse. Loss of blood group antigen expression is a stronger single indicator than is overexpression of the 01604 integrin. However, use of both markers together is a stronger predictive indicator than is either alone. We know little about the function of the blood group antigens in squamous cells except that the mature antigens are associated with differentiation. Similarly, the function of the a604 integrin is also not fully understood. Integrin a604 is thought to serve as an extracellular matrix receptor, but its ligand has not been confirmed. In resting epithelium, the a604 integrin is polarized to the basal aspect of the basal cell as a component of the hemidesmosome, the anchoring structures of the epithelia. This basal polarization is lost in migrating normal squamous cells and squamous carcinomas. Tyrosine phosphorylation of the 04 subunit is absent or greatly reduced in malignant cells and this may be a critical signal for subcellular localization of a604 and cell anchoring. On the basis of our current experimental results, we postulate that tyrosine phosphorylation of the 04 subunit is a reversible signal that regulates cell migration in normal and malignant cells, and may therefore be an important initial event in the metastatic cascade.