PROTEIN-KINASE-C INVOLVEMENT IN THE REGULATION OF ANGIOGENESIS

Using the chick chorioallantoic membrane as a model system for the study of angiogenesis, we have shown that promoters of protein kinase C (PKC) such as 4-beta-phorbol-12-myristate-13-acetate (4-beta-PMA) and 1,2-dioctanoyl-sn-glycerol (DiC8) stimulated angiogenesis. This effect was specific since 4-alpha-PMA and 1,2-dioleoyl-sn-glycerol, which either do not activate or cannot reach PKC, were devoid of angiogenic activity. Furthermore, Ro 31-8220, a specific inhibitor of PKC, suppressed both basal and 4-beta-PMA- or DiC8-induced angiogenesis. Similar results were obtained with the commonly used inhibitor of PKC, 1-(5-isoquinoline-sulfonyl)-2-methylpiperazine and with tricyclodecan-9-yl-xanthogenate, an antitumor agent which has been suggested to be an inhibitor of PKC. Activation of PKC may be, therefore, an important signalling pathway in the initiation and control of the angiogenic response.