Endothelial Cell-Specific Receptor Tie-2 as a Therapeutic Target

摘要

Angiopoietin-l (Ang-l) has been suggested to function as a promoter of physiological angiogenesis. We have investigated the potential role of Ang-l in breast cancer under clinical conditions and in experimental animals. Ang-l expression in breast cancer specimens was analyzed by using laser capture micro- dissection and RT-PCR. Cancer cells adjacent to micro-vessels expressing Tie-2 were dissected and analyzed. Ang-l mRNA was detected only in 3 of 21 cases and none of 9 normal specimens. The gene was then overexpressed in a human breast cancer cell line (MCF-7) by itself or together with FGF-l, which has been shown to enhance the angiogenic phenotype and tumorigenicity of this cell line. The overexpression of Ang-l had no effect on the growth of the transfected cells in culture. When inoculated in the mammary fat pads of female nude mice, however, Ang-l overexpressing cells exhibited markedly decreased tumorigenicity, and the growth rates of their xenograft tumors were significantly slower than that of the parental cells. These data support the view that Ang-l may function physiologically to promote angiogenesis by inducing vessel maturation and stabilization, but this may inhibit angiogenesis in tumor where the vasculature is highly immature and unstable.