POTENTIAL ANGIOGENIC ROLE OF PLATELET-ACTIVATING-FACTOR IN HUMAN BREAST-CANCER

This study investigated the presence of platelet-activating factor (PA F) in the lipid extracts of 18 primary breast carcinomas and 20 contro l breast tissues. The amount of PAF detected in breast carcinomas was significantly higher than in controls. The mass spectrometric analysis of PAF-bioactive lipid extract from breast carcinomas showed the pres ence of several molecular species of PAF, including C16-alkylPAF, C18- lysophosphatidylcholine (LPC), C16-LPC, lyso-PAF, and C16-acylPAF. The amount of bioactive PAF extracted from breast specimens significantly correlated with tumor vascularization revealed by the number of CD34- and CD31-positive cells. As C16-alkylPAF was previously shown to indu ce angiogenesis in vivo, we evaluated whether the thin layer chromatog raphy-purified lipid extracts of breast specimens elicited neoangiogen esis in a murine model of subcutaneous Matrigel injection. The lipid e xtracts from specimens of breast carcinoma containing high levels of P AF bioactivity, but not from breast carcinomas containing low levels o f PAF bioactivity of from normal breast tissue, induced a significant angiogenic response. This angiogenic response was significantly inhibi ted by the PAF receptor antagonist WEB 2170. T47D and MCF7 breast canc er cell Lines, but not an immortalized nontumor breast cell line (MCF1 0), released PAF in the culture medium. A significant in vivo neoangio genic response, inhibited by WEB 2170, was elicited by T47D and MCF7 b ut not by MCF10 culture medium These results indicate that an increase d concentration of PAF is present in tumors with high microvessel dens ity and that PAF may account for the neoangiogenic activity induced in mice by the lipid extracts obtained from breast cancer. A contributio n of PAF in the neovascularization of human breast cancer is suggested .