Identification of endosialin, a cell surface glycoprotein of vascular endothelial cells in human cancer Journal Article

   


Authors: Rettig, W. J.; Garin-Chesa, P.; Healey, J. H.; Su, S. L.; Jaffe, E. A.; Old, L. J.
Article Title: Identification of endosialin, a cell surface glycoprotein of vascular endothelial cells in human cancer
Abstract: Cell surface antigens of transformed cells are the traditional targets for antibody-guided detection and therapy of solid neoplasms. Alternative targets may be found in the tumor stroma, which contains newly formed blood vessels, reactive fibroblasts, and extracellular matrix proteins. The F19 cell surface glycoprotein of reactive fibroblasts is a prototypic stromal antigen since it is found in the stroma of >90% of common epithelial cancers but is absent or expressed at low levels in normal tissues and benign epithelial tumors. In the present study, we define an additional tumor stromal antigen, FB5, that is selectively expressed in vascular endothelial cells of malignant tumors. Immunohistochemical analysis of 128 tumors identified FB5 in endothelial cells in 67% of the samples (including 41 of 61 sarcomas, 26 of 37 carcinomas, and 18 of 25 neuroectodermal tumors) whereas normal blood vessels and other adult tissues tested lacked FB5 expression. In vitro studies showed that FB5 is a Mr 165,000 cell surface glycoprotein, comprised of a Mr 95,000 core polypeptide and highly sialylated O-linked oligosaccharides but few if any N-linked sugars, and that the FB5 gene is located on chromosome 11q13-qter. The restricted tissue distribution of the FB5 protein, which we refer to as endosialin, suggests strategies for tumor imaging and therapy that are aimed primarily at the tumor vasculature.
Keywords: immunohistochemistry; adult; controlled study; human tissue; human cell; nonhuman; neoplasms; antigen expression; protein analysis; mouse; animal; mice; protein targeting; interleukin 1beta; interleukin 4; neoplasm proteins; cell line; animal experiment; membrane proteins; tumor antigen; animalia; monoclonal antibody; endothelium cell; extracellular matrix; tumor necrosis factor alpha; gamma interferon; tissue distribution; vascular endothelium; endothelium, vascular; membrane glycoproteins; reference values; organ specificity; interleukin 6; chromosomes, human, pair 11; chromosome 11q; drug delivery system; gene location; chromosome mapping; cell surface protein; phorbol 13 acetate 12 myristate; tumor blood flow; sialylation; radioimmunoassay; basic fibroblast growth factor; protein glycosylation; hybrid cells; tumor stroma; forskolin; glycosylated protein; sialic acid; human; male; female; priority journal; article; support, non-u.s. gov't; support, u.s. gov't, p.h.s.; o-glycosylation
Journal Title: Proceedings of the National Academy of Sciences of the United States of America
Volume: 89
Issue: 22
ISSN: 0027-8424
Publisher: National Academy of Sciences  
Date Published: 1992-11-15
Start Page: 10832
End Page: 10836
Language: English
DOI: 10.1073/pnas.89.22.10832
PUBMED: 1438285
PROVIDER: scopus
PMCID: PMC50436
DOI/URL:

https://www.scopus.com/inward/record.uri?eid=2-s2.0-0026469991&doi=10.1073%2fpnas.89.22.10832&partnerID=40&md5=2d8335e0bd33a203488839b71bb11fb2
Notes: Source: Scopus
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MSK Authors
  1. John H Healey
    547 Healey
  2. Lloyd J Old
    593 Old
  3. Sai L Su
    21 Su
  4. Pilar Garin-Chesa
    73 Garin-Chesa
  5. Wolfgang J. Rettig
    85 Rettig
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