Endothelial cell response to human head and neck squamous cell carcinomas involves downregulation of protein...

Cancers, such as human head and neck squamous cell carcinomas (HNSCC), have been shown to stimulate angiogenesis by their production of endothelial cell proliferative and motility-stimulatory factors. The present studies to elucidate the intracellular mechanisms that contribute to the motility response of endothelial cells to HNSCC-derived factors showed a decline in the organization of actin filaments and microtubules. 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.