Structure and Function of VLA Integrins: Differential Expression in B-Cell Leukemia/Lymphoma

Abstract

The integrin family of adhesion receptors includes at least 11 different α subunits and 6 different β subunits which are associated to form 14 different αβ heterodimers, divided into three subfamilies. In particular, β1 subfamily integrins (VLA 1-6 proteins) have been found to mediate cell adhesion to extracellular matrix (ECM) component such as fibronectin, collagen, laminin; however, VLA-4 has been found to exhibit both cell-cell and cell-matrix adhesion functions. The reactivity of VLAs is virtually ubiquitous and independent of line or tissue specificity. However, the expression of individual VLAs within single tissues can be modulated according to the type or functional status of the cell.

One of the main reasons for interest in these molecules is that they may play a determining role in neoplastic transformation and diffusion; in particular, in lymphoproliferative syndromes, a lack of cell adhesiveness or an abnormal adhesion pattern in neoplastic lymphocytes may free these cells from regulation, thus contributing towards the development of leukemia and/or lymphoma. Studies of VLA expression in B-cell leukemia/lymphomas show a modulation of VLA3 and VLA4 reactivity. The most interesting element is the identification of a VLA3/VLA4 pattern associated with B-cell chronic lymphocytic leukemia (B-CLL) characterised by a reduced expression of VLA4 and the constant expression of VLA3. Although the value of VLA3 as an additional marker for the diagnosis of classical B-CLL is indisputable, the biological/functional significance of this reactivity remains to be confirmed.

Key Words:

• Integrins
• very late antigens (VLA)
• extracellular matrix (ECM)
• B-cell leukemia/lymphoma