Anti-CD105 Inhibits Primary Cancer Growth and Secondary Hematogenous Metastasis in a Xenograft Model

Abstract

CD105, a receptor for TGF-b1 and -b-3 modulates TGF-b signaling by interacting with TGF-bRI and/or II. It is now emerging as a prime vascular target of antiangiogenetic cancer therapy. In the present study, we investigate the efficacy of CD105 in colorectal cancer models. We found decreases in tumor size and in the number of metastatic foci to lung in a xenograft cancer model in scid mouse that was treated with Anti-CD105 antibody. The necrotic area in the tumor was greater in the anti-CD105 antibody group than that of the control group. The number of metastatic foci and the area of metastasis were also lesser in the anti-CD105 group than those of the control group. A direct effect of anti-CD105 antibody to the cultured colon cancer cell line was not detected in respect to morphology and proliferation. Decreased vasculature by an antiangiogenic effect of anti-CD105 antibody was confirmed by an immunohistochemical assessment of CD105 expression on frozen tumor tissue. These findings demonstrated that CD105 was specifically expressed in vascular endothelial cells in a xenograft colon cancer model, and anti-CD-105 antibody inhibited both tumor growth and hematogenous metastasis by blocking the vascular network. CD105 is a useful target and anti-CD105 antibody is a candidate for antiangiogenic colorectal cancer therapy.