Review Article
Head and Neck Oncology
Cell adhesion molecules, the extracellular matrix and oral squamous carcinoma

https://doi.org/10.1016/j.ijom.2007.04.002Get rights and content

Abstract

Carcinomas are characterized by invasion of malignant cells into the underlying connective tissue and migration of malignant cells to form metastases at distant sites. These processes require alterations in cell–cell and cell–extracellular matrix interactions. As cell adhesion molecules play a role in cell–cell and cell–extracellular matrix adhesion and interactions they are involved in the process of tumour invasion and metastases. In epithelial tissues, receptors of the integrin family mediate adhesion to the adjacent matrix whereas cadherins largely mediate intercellular adhesion. These and other cell adhesion molecules such as intercellular adhesion molecule-1, CD44, dystroglycans and selectins, are involved and undergo changes in carcinomas, which provide possible targets for anti-cancer drug treatments. In the extracellular matrix that is associated with tumours, laminin 5, oncofetal fibronectin and tenascin C appear. The degree of expression of some of these moieties indicates prognosis in oral cancer and offer targets for antibody-directed radiotherapy. Metalloproteases which degrade the extracellular matrix are increased in carcinomas, and their activity is necessary for tumour angiogenesis and consequent invasion and metastases. Metalloprotease inhibitors have begun to produce decreases in mortality in clinical trials. This report provides a brief overview of our current understanding of cell adhesion molecules, the extracellular matrix, tumour invasion and metastasis.

Section snippets

Integrins

The integrins (Fig. 1) represent the largest known family of cell adhesion molecules and are all integral membrane glycoproteins expressed in different combinations by all cells44. Integrins all consist of an α and a β subunit. Currently, 16 different α subunits, 8 β subunits and 24 combinations have been identified109. The two subunits collaborate to bind molecules in the extracellular matrix, the specificity of which is determined by the cell type and the subunit combination. Interactions

Collagens

Collagens are the commonest matrix molecule. Over 20 genetically distinct collagens have been identified. Paradoxically, despite being the commonest molecule of the matrix, few tumour-associated changes are apparent and these seem to be of little prognostic significance. Collagen IV is found only in the basement membrane in normal tissues, and in invasive tumours this molecule is found surrounding the carcinoma cells as they invade the matrix16. Collagen IV has been shown by

Conclusion

Over the past 20 years considerable progress has been made in understanding the nature of cell-surface membrane receptors, and the structure and dynamics of the extracellular matrix. This has led to a greater understanding of the process of tumour invasion and metastases, and undoubtedly to the identification of a number of prognostic indicators that may be useful in HNSCC. The use of antibodies to tumour-associated matrix molecules to concentrate radiotherapy around tumours is at a very early

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