Tumor growth and
metastasis are dependent on angiogenesis. Therefore, certain angiogenesis markers may be useful as
metastasis markers and/or the targets for antiangiogenic
therapy. We and others have been studying
endoglin(EDG; CD105) for such purposes. EDG is a proliferation-associated
antigen of endothelial cells and essential for angiogenesis. In addition, EDG is a component of the
transforming growth factor(
TGF)-beta receptor complex. Expression of EDG is up-regulated in
tumor-associated angiogenic vasculature compared with normal tissue vasculature. Microvessel density detected for EDG expression in
breast cancer tissues showed a statistically significant correlation with overall and disease-free survival. In addition, elevated serum EDG was associated with
metastasis in patients with colorectal, breast, and other solid
tumors. On the other hand, We have been targeting EDG on
tumor vasculature to suppress
tumor growth and
metastasis by systemic(i.v.) administration of anti-EDG
monoclonal antibodies(mAbs) and
immunoconjugates(IMCs). To thid end, we have been using three animal models, i.e., severe combined immunodeficient(SCID) mouse model of MCF-7 human
breast cancer, human skin/SCID mouse chimera model bearing MCF-7
tumor, and syngeneic
metastasis model of colon-26
adenocarcinoma cells in BALB/c mice. In addition, antiangiogenic activities of anti-EDG mAbs and IMCs were evaluated in mice using the dorsal air sac assay. The IMCs were prepared by coupling deglycosylated
ricin A-chain or 125I to individual anti-EDG mAbs. These anti-EDG IMCs and mAbs showed substantial antitumor efficacy and antimetastatic activities without showing severe toxicity. Recently, we generated a recombinant human/mouse chimeric anti-EDG mAb to facilitate clinical application of the mAb.