Identification of a high molecular weight endothelial cell surface glycoprotein, endoGlyx-1, in normal and tumor blood vessels.

BACKGROUND

The vascular endothelium participates in diverse physiologic and pathologic processes, ranging from blood clotting to leukocyte trafficking and tumor metastasis. Many of these functions are mediated by endothelial surface molecules, and monoclonal antibodies (mAb) have been used extensively to define endothelial cell surface structures in normal and lesional tissues.

EXPERIMENTAL DESIGN

MAbs raised against human umbilical vein endothelial cells were tested on a panel of cultured cell types representing diverse cell lineages. In vivo antigen expression was examined through immunohistochemical tests with normal and lesional tissues. Immunochemical methods were employed to characterize mAb-defined antigens in endothelial cell extracts.

RESULTS

The newly-derived mAbH572 reacts with a high molecular weight glycoprotein complex of cultured endothelial cells comprised of disulfide-bonded subunits of molecular weight 190,000, 140,000, 125,000, and 110,000. This antigen, designated endoGlyx-1, is expressed on the surface of cultured endothelium, with no changes in expression after cytokine-stimulation. Immunohistochemical assays detect endoGlyx-1 in endothelial cells of large, medium-sized, and small blood vessels, including capillaries, in all human organs tested; only hepatic and splenic sinusoids lack the molecule. EndoGlyx-1 is not found in any of the normal fetal and adult nonendothelial cell types tested. In a study of > 100 tumors, endoGlyx-1 immunostaining was consistently found in tumor capillaries, including "hot spots" of neoangiogenesis in certain tumors. EndoGlyx-1 is also expressed in hemangiomas and angiosarcomas.

CONCLUSIONS

The highly restricted expression of endoGlyx-1 in normal and tumor blood vessels suggests a role for this molecule unique to endothelial cell physiology. In fact, endoGlyx-1 appears to be the only endothelial lineage-specific cell surface glycoprotein identified to date. The availability of endoGlyx-1 antibodies may aid in the characterization and quantification of the angiogenic phase of solid tumors and facilitate the search for endothelial precursors in bone marrow or peripheral blood.