Understanding Metastasis Through Integrin Expression
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Integrins form a major family of heterodimeric cell surface receptors. Individual family members each comprise noncovalently linked, dissimilar, a- and β-subunits. Each subunit is the product of a different gene (1 ), and a-subunits appear to have evolved separately from β-subunits (2 ). Seventeen a-, and eight β-subunits are currently described. It is the combination of a- and β-subunits that gives rise to the individual family members. From this follows ligand-binding specificity, which may be relative (fibronectin has at least seven different binding sites), or absolute, (e.g., aEβ7 to E-cadherin [3 ]). High-affinity ligand recognition usually requires both subunits (4 ). The redundancy in this system, with many integrins binding the same ligand, suggests an important role in cellular communication in addition to heterotypic cell-cell (e.g., the β2 integrins and a4β1) or cell-extracellular matrix (most integrins) adhesion. In addition, some integrins bind microorganisms and certain plasma proteins. Moreover, integrins are involved in fundamental cellular events such as proliferation, differentiation, apoptosis, and motility. There is over whelming evidence for their fundamental role in the control of tumor differentia tion, proliferation, invasion and metastasis.
To better understand the biological significance of differential integrin expression in tumors it is first helpful to review the structure of integrin molecules, their diversity, and functional specialization. We will then discuss both the scientific methods commonly used and the experimental evidence that they have so far provided toward the understanding of the molecular control of tumor cell behavior.
