Therapeutic Regulation of Inflammation and Angiogenesis in Cancer, Arthritis, and Asthma, Sixth Annual Midwest Meeting, Chicago, IL, USA, March 16, 1998.

Abstract

The Sixth Annual Midwest Meeting of the Inflammation Research Association ‘Therapeutic Regulation of Inflammation and Angiogenesis in Cancer, Arthritis, and Asthma,’ was held in Chicago Illinois on March 16th, 1998. The meeting was organized and co-chaired by Drs. Keith Glaser, Stevan Djuric (both of Abbott Laboratories), and Jim Winkler (SmithKline Beecham). The symposium focused on two major topics, angiogenesis in inflammation and cancer, and the regulation of inflammatory processes. Both areas presented a broad-overview of pre-clinical and clinical development in these areas. The morning session was devoted to the topic of angiogenesis. Dr. Peter Polverini (University of Michigan, Ann Arbor, MI, USA) presented the first talk entitled an ‘Overview of Angiogenesis and Inflammation.’ He gave an overview of the process of angiogenesis and then focused on the role that inflammation plays in that process. Comparisons between tumor cells and psoriatic keratinocytes emphasized the importance these processes in maintaining a hyperproliferative response which ultimately requires the formation of new blood vessels for viability. He also reviewed the role of inflammatory cells, especially macrophages, in angiogenesis, then moved into a discussion of specific inflammatory/angiogenic molecules. He presented an overview of both angiogenesis inducers and inhibitors, including thrombospondin and interleukin 8. He also highlighted the balancing procedure that occurs during the act of induction/inhibition of angiogenesis. Stimulation of the macrophage appears to play a major role in this balancing procedure. The macrophage can stimulate angiogenesis by increasing VEGF and bFGF production or it can block angiogenesis by producing thrombospondin or IP-10. When stimulated by tumor cells or psoriatic keratinocytes, the macrophage decreases thrombospondin production thereby allowing angiogenesis to support cell growth. Thrombospondin’s specific effects on endothelial cells with regard to angiogenesis and apoptosis were covered to emphasize its major role in achieving the balance necessary to maintain tumor/hyperproliferative growth which also suggested some potential therapeutic targets for the future treatment of different diseases with major angiogenic components. Dr. Richard Kendall (Merck Pharmaceuticals, West Point, PA, USA) presented their recent work entitled ‘‘Effects of Inhibition of VEGF on Angiogenesis.’’ He reviewed the ligands (VEGF, PIGF) and receptors (Flt-1, KDR) that make up the vascular endothelial growth factor (VEGF) family. He then focused on work with soluble Flt-1, showing that it can bind ligand and can act as an inhibitor of the VEGF system. He showed that such inhibition could block the angiogenic process. Two mechanisms of action were discussed, sequestration of VEGF and the formation of non-functional heterodimers between soluble and intact receptors. These two mechanisms were demonstrated to inhibit tumor growth in vivo through the use of monoclonal antibodies directed against VEGF and through the expression of soluble Flt-1, respectively. The data presented demonstrated several alternative approaches to inhibition of the growth factor signaling pathway which were independent of inhibition of the receptor tyrosine kinase. Dr. Kevin Peters (Duke University, Durham, NC, USA) presented the third talk entitled ‘‘Effects of Inhibition of Tie2 Receptors on Angiogenesis and Cancer.’’ He reviewed the Tie2 ligands (angiopoietin-1 and angiopoietin-2) and receptor (Tie2 or Tek) system, then talked about the biology of soluble Tie2 receptor (Ex-Tek). Angiopoietin-1 increases Tie2 autophosphorylation but does not stimulate endothelial cell migration or tube formation. Angiopoietin-2 does not stimulate Tie2 autophosphorylation and acts as a natural antagonist of the angiopoietin-1/Tie2 system. The angiopoietin-1/Tie2 system perse is not angiogenic but functions to stabilize the mature vasculature. Therefore, interruption of this system can lead to destabilization and an anti-angiogenic Inflamm. res. 48 (1999) 101–103 Birkhauser Verlag, Basel, 1999