Abstract
Tumor vascularization is a complex process that requires structural reorganization and increased motility by endothelial cells. Studies were conducted to identify the tumor-derived mediators and signaling pathways that lead to this increased endothelial cell motility. Using the Lewis lung carcinoma (LLC) tumor model, these studies showed that prostaglandin E2 (PGE2) and transforming growth factor-β (TGFβ) were the mediators that were responsible for the migration-stimulatory activity produced by the tumor cells. The response of endothelial cells to these tumor-derived motility-stimulatory factors involved a decline in the activity of the serine/threonine phosphatase PP-2A. Inhibition PP-2A either pharmacologically or genetically increased endothelial cell migration. Concurrent with the decline in PP-2A activity as a result of exposure to PGE2/TGFβ was a loss of PP-2A co-precipitation with the inositol phosphatase PTEN and an increase in the PTEN serine phosphorylation level. Since hyperphosphorylation has been shown to inhibit the ability of PTEN to act as an antagonist to phosphatidylinositide 3-kinase (PI3K), the role of PI3K in PGE2/TGFβ-stimulated migration was examined. These studies showed that the increased endothelial cell motility that resulted from PGE2/TGFβ inhibition of PP-2A was dependent on PI3K.
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Young, M.R.I. Tumor-derived prostaglandin E2 and transforming growth factor-β stimulate endothelial cell motility through inhibition of protein phosphatase-2A and involvement of PTEN and phosphatidy linositide 3-kinase. Angiogenesis 7, 123–131 (2004). https://doi.org/10.1007/s10456-004-1027-2
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DOI: https://doi.org/10.1007/s10456-004-1027-2