Research
The Anti-angiogenic Effect of Tyrosine Kinase Inhibitors
Michihiko Kuwano
Professor, Dean, Faculty of Medical Sciences

What is angiogenesis ? Tumors cells need a rich blood supply in order to grow and metastasize. Angiogenesis is the process by which new blood vessels called capillaries are formed. Capillaries are lined with endothelial cells. Vascular endothelial growth factor receptor (VEGFR) inhibitor targets KDR tyrosine kinase. We demonstrated that a potent VEGFR tyrosine kinase inhibitor (VEGFR-TKI) also blocks Flt-1tyrosine kinase, which is another VEGF receptor. This compound inhibits migration of vascular endothelial cells and monocytes macrophages in response to placenta growth factor (PlGF). Moreover, this compound inhibits PlGF-induced angiogenesis in Matrigel plug assay. Anti-angiogenic activity of this compound appears to be due to inhibition of not only KDR but also Flt-1 tyrosine kinase. Epidermal growth factor receptor (EGFR) tyrosine kinase is a potential target for anticancer therapy. We demonstrated that the antitumor effects of EGFR tyrosine kinase inhibitor (EGFR-TKI) could be mediated in part by inhibition of tumor angiogenesis through direct effects on vascular endothelial cells (EGFR-TKI inhibited EGF-induced formation of tube-like structures ) and also through reduced production of proangiogenic factors (VEGF, IL-8) by tumor cells.

Dr. Michihiko Kuwano, Dean of Faculty of Medical Sciences explains here how the science battles with cancer. This research theme was chosen for one of the *P&P projects in 98-99. The research was carried out by the team of Schools of Medical Sciences, Pharmaceutical Sciences, Dental Science, Agriculture and Medical Institute of Bioregulation. *P&P: Kyushu University's grant for faculties to promote research and education, which started in 1997.