Functional involvement of CD44, a family of cell adhesion molecules, in immune responses, tumour progression and haematopoiesis

Cell-cell and cell-extracellular matrix (ECM) interactions play fundamental roles in many biological processes. Cells adhere to the ECM and to each other via specific cell surface receptors such as the selectins, integrins, Cadherins, members of the immunoglobulin superfamily, and of the CD44 superfamily. Surface molecules are necessary for cellular cross-talking and thus have a major impact on gene regulation, immune surveillance, immunological memory, motility, differentiation and growth control. Defined alterations in the cellular communication are features of embryonic development, immunobiology and neoplastic transformation. The model molecule and its functional analysis described here is the glycoprotein CD44 and its many isoforms. CD44 has been implicated to act in processes such as lymphocyte homing, haematopoiesis, tumour dissemination, lymphocyte activation, pattern formation in embryogenesis and inflammatory reactions. This multipurpose nature of CD44 can possibly be explained by the enormous number of isoforms. Although only encoded by one gene, CD44 represents a large family of molecules which differ in the primary structure. These differences are brought about by alternative splicing of at least ten unique exons, encoding extracellular regions. The function of the variant isoforms has been a matter of speculation for a long time, but now analysing mice which carry targeted mutations of specific exons a clearer picture is emerging