Adhesion Molecules in Cancer Biology
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ADHESION MOLECULES IN CANCER BIOLOGY Yaw Ohene-Abuakwa* and Massimo Pignatelli Division of Investigative Science Imperial College School of Medicine Hammersmith Campus Du Cane Road London Wl2 ONN INTRODUCTION Cell-cell and cell-extracellular matrix interactions profoundly influence a variety of biological processes such as cell growth, differentiation, and migration. A large number of transmembrane glycoproteins receptors namely Cell Adhesion Molecules (CAMs) and Substratum Adhesion Molecules (SAMs) which mediate adhesion between cells and/or between cells and extracellular matrix protein respectively have been identified. Their functions in many physiopathological processes have been studied using monoclonal antibodies, cell-cell and cell-substratum adhesion assays. It has become apparent that these molecules are expressed early during development on most cells and are subsequently maintained in a number of adult tissues derived from the three germ layers (Edelman and Crossin, 1991). Evidence from many laboratories suggests that adhesion molecules play important role in signal transduction processes (Howe et al., 1998), tumour progression and may promote tumour growth and organ-specific metastasis. Certain adhesion molecules may also function as tumour suppressor genes (Fawcett and Harris, 1992). It is now clear that many of the histopathological (e.g., loss of intercellular adhesion, derangement of cytological and architectural organisation) and behavioural features of neoplastic cells (e.g., invasion and metastasis) which constitute the basis of the classical morphological assessment may result from changes in adhesion molecule expression and/or function (Nigam et al., 1994; Pignatelli and Bodmer, 1988). Recent developments in cell and molecular biology techniques have led to the identification of five families of adhesion molecules which include the cadherins, integrins, immunoglobulin superfamily, selectins (Etter et al., 1997) and CD44 (Tuszynski et al., 1997). These receptors are genetically and biochemically distinct although, in some cases, are functionally related (Pignatelli, 1993b; Ruoslahti and Obrink, 1996).
*Tel/Fax: 0181 383 2432, e-mail: [email protected] Cancer Gene Therapy: Past Achievements and Future Challenges, edited by Habib Kluwer Academic / Plenum Publishers, New York, 2000.
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Y. Ohene-Abuakwa and M. Pignatelli
In this chapter we describe recent data on the role of selected CAMs and SAMs in normal tissues and the evidence implicating them in key aspects of tumour biology including differentiation, invasion and metastasis.
INTEGRINS Integrins are transmembrane glycoproteins comprising of 16 alpha and 9 beta subunits which form at least 22 different non-covalently heterodimers involved in cell-cell and cell-matrix interactions. Originally, Hynes (1987) divided integrins into three main subfamilies capable of associating with specific groups of subunits, but more recent work has shown that some subunits can associate with more than one subunit, making this classification mo
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