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Abstract

We investigated whether tumor cell/endothelia interaction can be influenced by platelet-activating factor (PAF, 1-O-alkyl-2-acetyl-sn-glycero-3-phosphocholine), a lipid mediator that promotes adhesiveness and extravasation of leukocytes in the inflammatory reaction. We found that the PAF receptor antagonist WEB 2086 prevents adhesion of melanoma Hs294T and colon carcinoma LS180 lines to IL-1-stimulated endothelial cells. Moreover, PAF stimulated the adhesiveness of Hs294T and LS180 cells to VCAM-1 and E- selectin, respectively, in an artificial model consisting of recombinant adhesive proteins bound to protein A-coated substrata. Thus, tumoral and not endothelial cell surface seems to be involved in the PAF-mediated enhancement of tumor cell adhesiveness to IL-1-activated endothelia. This observation is supported by the finding that Hs294T and LS180 cells express high affinity and functionally active receptors for PAF. By using specific inhibitors, we found that PAF-induced enhancement of cell adhesiveness was mediated by G-protein activation and protein tyrosine phosphorylation. In addition, protein tyrosine phosphorylation was observed in Hs294T and LS180 cells stimulated by PAF. In conclusion, we demonstrated that PAF-mediated activation of tumor cells enhances their adhesiveness to IL-1-stimulated vascular endothelia.

Clopidogrel in a combined therapy with anticancer drugs—effect on tumor growth, metastasis, and treatment toxicity: Studies in animal models

“…Interactions of activated platelets with tumor cells promote the adhesion of the latter to the vascular endothelial cells in the target tissue, which precedes the process of extravasation and eventual invasion into the colonized tissues. The molecular mechanism mediating this process is based primarily on selectin-mediated interactions [ 14 , 15 ], however, other factors of platelet origin, such as platelet activating factor (PAF) have also been shown to facilitate extravasation [ 16 , 17 ]. Finally, platelets contribute to pre-metastatic niche formation and thus indirectly favor cancer cells extravasation [ 12 ].…”

Platelet-activating Factor Mediates MMP-2 Expression and Activation via Phosphorylation of cAMP-response Element-binding Protein and Contributes to Melanoma Metastasis

“…In addition, intraperitoneally injected PAF promoted experimental lung metastasis of B16F10 cells (34). PAF mediated the adhesiveness of Hs294T human melanoma cells and LS180 human colon cancer cells to IL-1-stimulated endothelial cells (35). Vascular endothelial growth factor, basic fibroblast growth factor, hepatocyte growth factor, tumor necrosis factor-␣, and thrombin have been shown to induce PAF production by human breast cancer cells in vitro and to induce PAF-dependent cell proliferation (36).…”

Lipoprotein-Associated Phospholipase A2: A Novel Contributor in Sjögren’s Syndrome-Related Lymphoma?

“…In patients with prostate cancer, Lp-PLA2 has been shown to promote cancer cell migration and invasion, possibly through generation of oxidized nonesterified fatty acids and lysophosphatidylcholine (LPC) (38). The latter is a phospholipid derivative following hydrolysis of oxidized phospholipids by Lp-PLA2 and has been previously shown to augment cell-to-cell adhesion molecules on endothelial cells, induce migration and proliferation of smooth muscle cells (39,40) and along with oxidized non esterified fatty acids promote inflammatory effects (41). Collectively, these data reinforce the idea of the contribution of the inflammatory microenvironment in promoting malignant transformation.…”