The human myoepithelial cell displays a multifaceted anti-angiogenic phenotype

Human myoepithelial cells which surround ducts and acini of certain organs such as the breast form a natural border separating epithelial cells from s tromal angiogenesis. Myoepithelial cell lines (HMS-1-6), derived from diver se benign myoepithelial tumors, all constitutively express high levels of a ctive angiogenic inhibitors which include TIMP-1, thrombospondin-1 and solu ble bFGF receptors but very low levels of angiogenic factors. These myoepit helial cell lines inhibit endothelial cell chemotaxis and proliferation. Th ese myoepithelial cell lines sense hypoxia, respond to low O-2 tension by i ncreased HIF-1 alpha but with only a minimal increase in VEGF and iNOS stea dy state mRNA levels. Their corresponding xenografts (HMS-X-6X) grow very s lowly compared to their non-myoepithelial carcinomatous counterparts and ac cumulate an abundant extracellular matrix devoid of angiogenesis but contai ning bound angiogenic inhibitors. These myoepithelial xenografts exhibit on ly minimal hypoxia but extensive necrosis in comparison to their non-myoepi thelial xenograft counterparts. These former xenografts inhibit local and s ystemic tumor-induced angiogenesis and metastasis presumably from their mat rix-bound and released circulating angiogenic inhibitors. These observation s collectively support the hypothesis that the human myoepithelial cell (ev en when transformed) is a natural suppressor of angiogenesis.