Angiogenesis, the formation of new blood vessels, is crucial to a number of physiological processes such as reproduction, development and tissue repair, as well as in disease states including cancer, rheumatoid arthritis and other inflammatory diseases. Consequently angiogenesis represents an emerging therapeutic target which by 2006, is expected to command a market of $1.75 billion. Angiogenesis is a well-programmed cascade of events, which contains a number of distinct steps. In our previous edition of TherapeuticAdvances, we focussed on the integrins, and in particular alpha(5)beta(1) and its antagonist ATN-161, which are involved in the migration and adhesion of endothelial (click here for abstract).

In this edition we focus on research emerging from the Chinese Academy of Sciences which set out to raise monoclonal antibodies (mAbs) against endothelial cell surface proteins specific for tumor vasculature. One particular antibody mAb AA98 showed remarkably restricted immunoreactivity against intratumoral neovasculature compared to blood vessels of normal tissues. The AA98-antigen was identified as human CD146 (Melanoma-associated adhesion molecule MUC18/MCAM), an adhesion molecule belonging to the immunoglobulin superfamily. Data from in vitro experiments imply structural and signaling functions for endothelial CD146, however, the role of CD146 in vivo is largely unknown. This study reported that mAb AA98 displays anti-angiogenic properties in vitro and in vivo. Proliferation and migration of HUVECs were inhibited by mAb AA98 as was angiogenesis in chicken chorioallantoic membrane assays and tumor growth in three xenografted human tumor models in mice. These data provide new insights into the function of CD146 on endothelial cells, validate CD146 as a novel target for antiangiogenic agents, and demonstrate that mAb AA98 has potential as a diagnostic and therapeutic agent in vascular and cancer biology.

Of interest, inhibitors of angiogenesis are receiving growing attention with respect to their potential to treat arthritis (click here to access our recent DiscoveryDossier focusing on this field). One molecular target is CD146, levels of which are increased in the joints of patients with rheumatoid arthritis and hence molecules that target this adhesion molecule may serve to limit synovial vascularization and limit the development of arthritis.

Entry date Friday, April 11, 2003

Adapted from Yan et al, Blood 2003 Feb 27; [epub ahead of print] - Interested in collaborating with this group? Contact LeadDiscovery or the authors direct.

Interested in collaborating with this group? Contact leaddiscovery@bioportfolio.co.uk