Lack of specificity of endoglin expression for tumor blood vessels

Abstract

A monoclonal antibody (MAb; A11) has been raised following mouse immunization with cultured human microvascular endothelial cells. The MAb showed a strong 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 developed starting from DG-RSV-LT-2, an immortalized human endothelial cell line. Molecular mass, N-terminal sequence of the purified antigen and localization on endothelial cell surface allowed identification with human endoglin (CD105). Flow cytometry analysis of a group of normal and transformed cell lines showed that, besides endothelial cells and myelocytic leukemia cells already shown to be positive, fetal fibroblasts, choriocarcinoma, fibrosarcoma 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 described with previously characterized antibodies. In fact, even though the staining was weaker than in tumor tissues, all tissues were found to be positive, at least in microvessels, except for normal breast. Moreover, in some tissues (glands and reproductive tract) a positive reaction was observed in the stroma. Since endoglin has been proposed as a possible target for antiangiogenic therapy in tumor patients and our data demonstrate a sizable amount of endoglin in normal vessels and stroma, its clinical use should be carefully reevaluated.

Nestin Is Expressed in Vascular Endothelial Cells in the Adult Human Pancreas

“…These cells varied in staining intensity and had often a stroma-like appearance. It has been reported that, in some tissues, endoglin and CD34 mark not only vascular endothelial cells but also fibroblasts and leukocytes, which could explain the additional occurrence of endoglin-positive/nestin-negative and CD34-positive/nestin-negative cells (Nakayama et al 2000;Balza et al 2001;O'Connell et al 1992). However, it can neither be excluded that a minute number of PECAM-1, CD34, and endoglin-positive endothelial cells of small blood vessels do not express nestin nor that nestin is expressed in a small subpopulation of non-endothelial cells that are also positive for the tested endothelial markers.…”

The Extra-domain A of Fibronectin Is a Vascular Marker of Solid Tumors and Metastases

“…For instance, endoglin has long been known to be overexpressed in the tumor neovasculature (see, e.g., ref. 6), although its expression in normal organs is not negligible (32).…”

Chronic idiopathic myelofibrosis: independent prognostic importance of bone marrow microvascular density evaluated by CD105 (endoglin) immunostaining

“…CD105 is preferentially expressed by recently formed vessels, 11,49 although nonspecific. 49,50 The presence of CD105-positive MVD appears to worsen the prognosis of patients with CIMF. The potential therapeutic use of anti-CD105 immunotherapy in CIMF deserves investigation, particularly in the group of CIMF patients with highest CD105-MVD values.…”