ENDOTHELIAL-CELL RESPONSE TO HUMAN HEAD AND NECK SQUAMOUS-CELL CARCINOMAS INVOLVES DOWN-REGULATION OF PROTEIN PHOSPHATASES-1 2A, CYTOSKELETAL DEPOLYMERIZATION AND INCREASED MOTILITY/

Cancers, such as human head and neck squamous cell carcinomas (HNSCC), have been shown to stimulate angiogenesis by their production of endo thelial cell proliferative and motility-stimulatory factors. The prese nt studies to elucidate the intracellular mechanisms that contribute t o the motility response of endothelial cells to HNSCC-derived factors showed a decline in the organization of actin filaments and microtubul es, This HNSCC-induced decline in cytoskeletal organization coincided with the downregulation of endothelial cell protein phosphatase-1 and 2A (PP-1/2A) activities, and could be mimicked by directly inhibiting these enzyme activities with okadaic acid. These results show that the increased motility of endothelial cells in response to HNSCC-derived angiogenic factors involves downregulation of PP-1/2A activities and, consequently, a decline in cytoskeletal organization.