Lack of specificity of endoglin expression for tumor blood vessels

A monoclonal antibody (MAb; A11) has been raised following mouse immunizati on with cultured human microvascular endothelial cells. The MAb showed a st rong positivity within tumor vessels in glioblastoma. and breast carcinoma samples, and the distribution was consistent with antigen association with vascular endothelial cells. A purification procedure of the antigen was dev eloped starting from DG-RSV-LT-2, an immortalized human endothelial cell li ne. Molecular mass, N-terminal sequence of the purified antigen and localiz ation on endothelial cell surface allowed identification with human endogli n (CD105). Flow cytometry analysis of a group of normal and transformed cel l lines showed that, besides endothelial cells and myelocytic leukemia cell s already shown to be positive, fetal fibroblasts, choriocarcinoma, fibrosa rcoma and rhabdomyosarcoma cell lines were also positive for this antigen. Immunohistochemic analysis of several normal adult tissues revealed a more extensive presence of the antigen in normal vessels compared to that descri bed with previously characterized antibodies. In fact, even though the stai ning was weaker than in tumor tissues, all tissues were found to be positiv e, at least in microvessels, except for normal breast. Moreover, in some ti ssues (glands and reproductive tract) a positive reaction was observed in t he stroma. Since endoglin has been proposed as a possible target for antian giogenic therapy in tumor patients and our data demonstrate a sizable amoun t of endoglin in normal vessels and stroma, its clinical use should be care fully reevaluated. (C) 2001 Wiley-Liss, Inc.