Seprase Promotes Rapid Tumor Growth and Increased Microvessel Density in a Mouse Model of Human Breast Cancer

Abstract

Seprase is a cell surface serine protease that is expressed to high levels by invading human breast carcinoma cells. To investigate the role of seprase in breast cancer, MDA MB-231 human mammary adenocarcinoma cells were engineered to express active seprase to high levels. All cells grow rapidly in cell culture. But differences are discovered when the cells are tested for tumorigenicity, growth, and microvessel density by implantation into the mammary fat pads of female severe combined immunodeficient mice. Control transfectants that do not express seprase grow slowly whereas cells that express seprase to high levels form fast-growing tumors that are highly vascular. Microvessel density is elevated in tumors of two different lines of seprase transfectants to 146 +/- 67.4 and 144 +/- 33.42 vessels/mm(2) as compared with 50.5 +/- 12.9 vessels/mm(2) for tumors of control-transfected cells that do not express seprase. Seprase-expressing cells are better able to attract blood vessels and exhibit rapid tumor growth.