Bussolati B, Biancone L, Cassoni P, Russo S, Rola-Pleszczynski M, Montrucchio G, Camussi G
Department of Internal Medicine, University of Torino, Torino, Italy.
Am J Pathol. 2000 Nov;157(5):1713-25. doi: 10.1016/S0002-9440(10)64808-0.
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 synthesized within breast cancer. In vitro, we observed the production of PAF by two estrogen-dependent (MCF7 and T-47D) and an estrogen-independent (MDA-MB231) breast cancer cell lines after stimulation with vascular endothelial 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 synthesized as cell-associated or released varied in different cell lines, being higher in MDA-MB231 cells, which are known to be highly invasive. We further demonstrate, by reverse transcriptase-polymerase chain reaction and cytofluorimetry, 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 formation of new vessels in a tumor induced by subcutaneous implantation of MDA-MB231 cells into SCID mice. In conclusion, these results suggest that PAF, produced and released by breast cancer cells, can contribute to tumor development by enhancing cell motility and proliferation and by stimulating the angiogenic response.
血小板活化因子（PAF）是一种炎症的磷脂介质，存在于乳腺癌组织中，并与微血管密度相关。在本研究中，我们调查了乳腺癌内合成的PAF的生物学意义。在体外，我们观察了两种雌激素依赖性（MCF7和T-47D）和一种雌激素非依赖性（MDA-MB231）乳腺癌细胞系在受到血管内皮生长因子、碱性成纤维细胞生长因子、肝细胞生长因子、肿瘤坏死因子、凝血酶刺激后PAF的产生情况，但雌激素、孕酮和催产素刺激后未观察到PAF产生。不同细胞系对激动剂刺激的敏感性以及作为细胞相关或释放的PAF合成量各不相同，在已知具有高度侵袭性的MDA-MB231细胞中更高。我们通过逆转录聚合酶链反应和细胞荧光分析进一步证明，所有乳腺癌细胞均表达PAF受体，并在增殖方面对PAF刺激有反应。此外，在MDA-MB231细胞中，PAF引起细胞运动。在体内，两种结构不同的PAF受体拮抗剂WEB 2170和CV 3988显著减少了将MDA-MB231细胞皮下植入SCID小鼠诱导的肿瘤中新生血管的形成。总之，这些结果表明，乳腺癌细胞产生和释放的PAF可通过增强细胞运动和增殖以及刺激血管生成反应来促进肿瘤发展。
