Skip to main content
NCBI home page
Proceedings of the National Academy of Sciences of the United States of America logoLink to Proceedings of the National Academy of Sciences of the United States of America
. 1992 Mar 15;89(6):2292–2296. doi: 10.1073/pnas.89.6.2292

Granule membrane protein 140 (GMP140) binds to carcinomas and carcinoma-derived cell lines.

A Aruffo 1, M T Dietsch 1, H Wan 1, K E Hellström 1, I Hellström 1
PMCID: PMC48643  PMID: 1372439

Abstract

The glycoproteins granule membrane protein 140 (GMP140), endothelial-leukocyte adhesion molecule 1 (ELAM-1), and Leu-8 are members of a family of glycoprotein receptors (selectins or LEC-CAMs) that play an important role in adhesive interactions between circulating leukocytes and vascular endothelium. Recently it has been reported that ELAM-1 is able to mediate the binding of the colon carcinoma cell line HT-29 to cytokine-activated vascular endothelium, suggesting that tumor cell adhesion to vascular endothelium, a prerequisite for tumor extravasation and metastasis, is in part the result of adhesive interactions between blood-borne tumor cells and cell surface proteins expressed by vascular endothelium. Here, using an approach in which soluble immunoglobulin chimeras of the GMP140 and ELAM-1 receptors were prepared and used to carry out immunohistological studies, we establish that GMP140 binds to tumor cells in a variety of human carcinoma tissue sections (colon, lung, and breast), whereas ELAM-1 binds exclusively to tumor cells in colon carcinoma tissue sections. In addition, GMP140 was found to bind to the cell surface of a number of cell lines derived from various carcinomas but not from melanomas, whereas ELAM-1 bound only colon carcinoma cell lines. We further investigated the nature of the ligands of GMP140 and ELAM-1 on the surface of the carcinoma cells and found that the GMP140 ligand on the surface of tumor cells appears to be distinct from that expressed on the myeloid cell line HL-60. Neuraminidase treatment of a breast carcinoma cell line does not affect, or in some instances increases, GMP140 binding, whereas it completely abolishes GMP140 binding to HL-60 cells. On the other hand, the ligand of ELAM-1 on both the colon carcinoma and HL-60 cells is neuraminidase sensitive in accord with its identification as sialyl-CD15. Parallel results were obtained with neuraminidase-treated frozen carcinoma tissue sections. The present findings form the basis for investigating the role of GMP140 in tumor invasiveness and metastasis.

Full text

PDF
2292

Images in this article

2293Image
on p.2293
2294Image
on p.2294

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Aruffo A., Kolanus W., Walz G., Fredman P., Seed B. CD62/P-selectin recognition of myeloid and tumor cell sulfatides. Cell. 1991 Oct 4;67(1):35–44. doi: 10.1016/0092-8674(91)90570-o. [DOI] [PubMed] [Google Scholar]
  2. Bevilacqua M. P., Pober J. S., Mendrick D. L., Cotran R. S., Gimbrone M. A., Jr Identification of an inducible endothelial-leukocyte adhesion molecule. Proc Natl Acad Sci U S A. 1987 Dec;84(24):9238–9242. doi: 10.1073/pnas.84.24.9238. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Bevilacqua M. P., Stengelin S., Gimbrone M. A., Jr, Seed B. Endothelial leukocyte adhesion molecule 1: an inducible receptor for neutrophils related to complement regulatory proteins and lectins. Science. 1989 Mar 3;243(4895):1160–1165. doi: 10.1126/science.2466335. [DOI] [PubMed] [Google Scholar]
  4. Billaud M., Rousset F., Calender A., Cordier M., Aubry J. P., Laisse V., Lenoir G. M. Low expression of lymphocyte function-associated antigen (LFA)-1 and LFA-3 adhesion molecules is a common trait in Burkitt's lymphoma associated with and not associated with Epstein-Barr virus. Blood. 1990 May 1;75(9):1827–1833. [PubMed] [Google Scholar]
  5. Bonfanti R., Furie B. C., Furie B., Wagner D. D. PADGEM (GMP140) is a component of Weibel-Palade bodies of human endothelial cells. Blood. 1989 Apr;73(5):1109–1112. [PubMed] [Google Scholar]
  6. Camerini D., James S. P., Stamenkovic I., Seed B. Leu-8/TQ1 is the human equivalent of the Mel-14 lymph node homing receptor. Nature. 1989 Nov 2;342(6245):78–82. doi: 10.1038/342078a0. [DOI] [PubMed] [Google Scholar]
  7. Corral L., Singer M. S., Macher B. A., Rosen S. D. Requirement for sialic acid on neutrophils in a GMP-140 (PADGEM) mediated adhesive interaction with activated platelets. Biochem Biophys Res Commun. 1990 Nov 15;172(3):1349–1356. doi: 10.1016/0006-291x(90)91598-m. [DOI] [PubMed] [Google Scholar]
  8. Ey P. L., Prowse S. J., Jenkin C. R. Isolation of pure IgG1, IgG2a and IgG2b immunoglobulins from mouse serum using protein A-sepharose. Immunochemistry. 1978 Jul;15(7):429–436. doi: 10.1016/0161-5890(78)90070-6. [DOI] [PubMed] [Google Scholar]
  9. Garrigues H. J., Tilgen W., Hellstróm I., Franke W., Hellström K. E. Detection of a human melanoma-associated antigen, p97, in histological sections of primary human melanomas. Int J Cancer. 1982 May 15;29(5):511–515. doi: 10.1002/ijc.2910290505. [DOI] [PubMed] [Google Scholar]
  10. Geng J. G., Bevilacqua M. P., Moore K. L., McIntyre T. M., Prescott S. M., Kim J. M., Bliss G. A., Zimmerman G. A., McEver R. P. Rapid neutrophil adhesion to activated endothelium mediated by GMP-140. Nature. 1990 Feb 22;343(6260):757–760. doi: 10.1038/343757a0. [DOI] [PubMed] [Google Scholar]
  11. Goelz S. E., Hession C., Goff D., Griffiths B., Tizard R., Newman B., Chi-Rosso G., Lobb R. ELFT: a gene that directs the expression of an ELAM-1 ligand. Cell. 1990 Dec 21;63(6):1349–1356. doi: 10.1016/0092-8674(90)90430-m. [DOI] [PubMed] [Google Scholar]
  12. Günthert U., Hofmann M., Rudy W., Reber S., Zöller M., Haussmann I., Matzku S., Wenzel A., Ponta H., Herrlich P. A new variant of glycoprotein CD44 confers metastatic potential to rat carcinoma cells. Cell. 1991 Apr 5;65(1):13–24. doi: 10.1016/0092-8674(91)90403-l. [DOI] [PubMed] [Google Scholar]
  13. Hellström I., Garrigues H. J., Garrigues U., Hellström K. E. Highly tumor-reactive, internalizing, mouse monoclonal antibodies to Le(y)-related cell surface antigens. Cancer Res. 1990 Apr 1;50(7):2183–2190. [PubMed] [Google Scholar]
  14. Hsu-Lin S., Berman C. L., Furie B. C., August D., Furie B. A platelet membrane protein expressed during platelet activation and secretion. Studies using a monoclonal antibody specific for thrombin-activated platelets. J Biol Chem. 1984 Jul 25;259(14):9121–9126. [PubMed] [Google Scholar]
  15. Johnston G. I., Cook R. G., McEver R. P. Cloning of GMP-140, a granule membrane protein of platelets and endothelium: sequence similarity to proteins involved in cell adhesion and inflammation. Cell. 1989 Mar 24;56(6):1033–1044. doi: 10.1016/0092-8674(89)90636-3. [DOI] [PubMed] [Google Scholar]
  16. Larsen E., Celi A., Gilbert G. E., Furie B. C., Erban J. K., Bonfanti R., Wagner D. D., Furie B. PADGEM protein: a receptor that mediates the interaction of activated platelets with neutrophils and monocytes. Cell. 1989 Oct 20;59(2):305–312. doi: 10.1016/0092-8674(89)90292-4. [DOI] [PubMed] [Google Scholar]
  17. Lowe J. B., Stoolman L. M., Nair R. P., Larsen R. D., Berhend T. L., Marks R. M. ELAM-1--dependent cell adhesion to vascular endothelium determined by a transfected human fucosyltransferase cDNA. Cell. 1990 Nov 2;63(3):475–484. doi: 10.1016/0092-8674(90)90444-j. [DOI] [PubMed] [Google Scholar]
  18. McEver R. P., Beckstead J. H., Moore K. L., Marshall-Carlson L., Bainton D. F. GMP-140, a platelet alpha-granule membrane protein, is also synthesized by vascular endothelial cells and is localized in Weibel-Palade bodies. J Clin Invest. 1989 Jul;84(1):92–99. doi: 10.1172/JCI114175. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. McEver R. P., Martin M. N. A monoclonal antibody to a membrane glycoprotein binds only to activated platelets. J Biol Chem. 1984 Aug 10;259(15):9799–9804. [PubMed] [Google Scholar]
  20. Moore K. L., Varki A., McEver R. P. GMP-140 binds to a glycoprotein receptor on human neutrophils: evidence for a lectin-like interaction. J Cell Biol. 1991 Feb;112(3):491–499. doi: 10.1083/jcb.112.3.491. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Ord D. C., Ernst T. J., Zhou L. J., Rambaldi A., Spertini O., Griffin J., Tedder T. F. Structure of the gene encoding the human leukocyte adhesion molecule-1 (TQ1, Leu-8) of lymphocytes and neutrophils. J Biol Chem. 1990 May 15;265(14):7760–7767. [PubMed] [Google Scholar]
  22. Patel K. D., Zimmerman G. A., Prescott S. M., McEver R. P., McIntyre T. M. Oxygen radicals induce human endothelial cells to express GMP-140 and bind neutrophils. J Cell Biol. 1991 Feb;112(4):749–759. doi: 10.1083/jcb.112.4.749. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Phillips M. L., Nudelman E., Gaeta F. C., Perez M., Singhal A. K., Hakomori S., Paulson J. C. ELAM-1 mediates cell adhesion by recognition of a carbohydrate ligand, sialyl-Lex. Science. 1990 Nov 23;250(4984):1130–1132. doi: 10.1126/science.1701274. [DOI] [PubMed] [Google Scholar]
  24. Picker L. J., Kishimoto T. K., Smith C. W., Warnock R. A., Butcher E. C. ELAM-1 is an adhesion molecule for skin-homing T cells. Nature. 1991 Feb 28;349(6312):796–799. doi: 10.1038/349796a0. [DOI] [PubMed] [Google Scholar]
  25. Polley M. J., Phillips M. L., Wayner E., Nudelman E., Singhal A. K., Hakomori S., Paulson J. C. CD62 and endothelial cell-leukocyte adhesion molecule 1 (ELAM-1) recognize the same carbohydrate ligand, sialyl-Lewis x. Proc Natl Acad Sci U S A. 1991 Jul 15;88(14):6224–6228. doi: 10.1073/pnas.88.14.6224. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Rice G. E., Bevilacqua M. P. An inducible endothelial cell surface glycoprotein mediates melanoma adhesion. Science. 1989 Dec 8;246(4935):1303–1306. doi: 10.1126/science.2588007. [DOI] [PubMed] [Google Scholar]
  27. Shimizu Y., Shaw S., Graber N., Gopal T. V., Horgan K. J., Van Seventer G. A., Newman W. Activation-independent binding of human memory T cells to adhesion molecule ELAM-1. Nature. 1991 Feb 28;349(6312):799–802. doi: 10.1038/349799a0. [DOI] [PubMed] [Google Scholar]
  28. Siegelman M. H., Cheng I. C., Weissman I. L., Wakeland E. K. The mouse lymph node homing receptor is identical with the lymphocyte cell surface marker Ly-22: role of the EGF domain in endothelial binding. Cell. 1990 May 18;61(4):611–622. doi: 10.1016/0092-8674(90)90473-r. [DOI] [PubMed] [Google Scholar]
  29. Stoolman L. M. Adhesion molecules controlling lymphocyte migration. Cell. 1989 Mar 24;56(6):907–910. doi: 10.1016/0092-8674(89)90620-x. [DOI] [PubMed] [Google Scholar]
  30. Tiemeyer M., Swiedler S. J., Ishihara M., Moreland M., Schweingruber H., Hirtzer P., Brandley B. K. Carbohydrate ligands for endothelial-leukocyte adhesion molecule 1. Proc Natl Acad Sci U S A. 1991 Feb 15;88(4):1138–1142. doi: 10.1073/pnas.88.4.1138. [DOI] [PMC free article] [PubMed] [Google Scholar]
  31. Walz G., Aruffo A., Kolanus W., Bevilacqua M., Seed B. Recognition by ELAM-1 of the sialyl-Lex determinant on myeloid and tumor cells. Science. 1990 Nov 23;250(4984):1132–1135. doi: 10.1126/science.1701275. [DOI] [PubMed] [Google Scholar]
  32. Zetter B. R. The cellular basis of site-specific tumor metastasis. N Engl J Med. 1990 Mar 1;322(9):605–612. doi: 10.1056/NEJM199003013220907. [DOI] [PubMed] [Google Scholar]

Articles from Proceedings of the National Academy of Sciences of the United States of America are provided here courtesy of National Academy of Sciences

RESOURCES