PAF produced by human breast cancer cells promotes migration and proliferation of tumor cells and neo-angiogenesis

Platelet-activating factor (PAF), a phospholipid mediator of inflammation, Is present in breast cancer tissue and correlates with microvessel density. In the present study, we investigated the biological significance of PAF s ynthesized within breast cancer. In vitro, we observed the production of PA F by two estrogen-dependent (MCF7 and T-47D) and an estrogen-independent (M DA-MB231) breast cancer cell lines after stimulation with vascular endothel ial growth factor, basic fibroblast growth factor, hepatocyte growth factor , tumor necrosis factor, thrombin but not with estrogen, progesterone, and oxytocin. The sensitivity to agonist stimulation and the amount of PAF synt hesized as cell-associated or released varied in different cell lines, bein g higher In MDA-MB231 cells, which are known to be highly invasive. We furt her demonstrate, by reverse transcriptase-polymerase chain reaction and cyt ofluorimetry, that all of the breast cancer cells express the PAF receptor and respond to PAF stimulation in terms of proliferation. Moreover, in MDA- MB231 cells PAF elicited cell motility. In vivo, two structurally different PAF receptor antagonists WEB 2170 and CV 3988 significantly reduced the fo rmation of new vessels In a tumor induced by subcutaneous implantation of M DA-MB231 cells into SCID mice. In conclusion, these results suggest that DA F, produced acid released by breast cancer cells, can contribute to tumor d evelopment by enhancing cell motility and proliferation and by stimulating the angiogenic response.