Abstract
Activated platelets and stimulated endothelial cells express P-selectin, an integral membrane protein receptor that binds monocytes and neutrophils. P-selectin mediates adhesion to glycoproteins with carbohydrate structures containing sialyl-Lewis X. Since many carcinoma cells also express these carbohydrate structures and are known to interact with platelets, we asked whether P-selectin may mediate this interaction. Both small cell lung cancer and neuroblastoma cell lines bound to activated platelets, and this interaction was blocked with inhibitory anti-P-selectin antibodies and by pretreatment of these cancer cells with neuraminidase or trypsin. Platelet binding to the small cell lung cancer cells was not inhibited with anti-GP IIb-IIIa antibody or Arg-Gly-Asp-Ser peptide. Pretreatment of the neuroblastoma cells with inhibitors of N-linked carbohydrate biosynthesis had little effect on binding to P-selectin, indicating that relevant carbohydrate ligand(s) may be O-linked. In addition, lipospheres containing P-selectin specifically bound to cryostat sections derived from a small cell lung tumor and two neuroblastoma tumors, but not to sections of normal lung. These observations demonstrate that P-selectin mediates binding of platelets to small cell lung cancer and to neuroblastoma and suggest a possible role for this lectin in metastasis.
Full text
PDF









Images in this article
Selected References
These references are in PubMed. This may not be the complete list of references from this article.
- Aruffo A., Dietsch M. T., Wan H., Hellström K. E., Hellström I. Granule membrane protein 140 (GMP140) binds to carcinomas and carcinoma-derived cell lines. Proc Natl Acad Sci U S A. 1992 Mar 15;89(6):2292–2296. doi: 10.1073/pnas.89.6.2292. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 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]
- Bastida E., Ordinas A. Platelet contribution to the formation of metastatic foci: the role of cancer cell-induced platelet activation. Haemostasis. 1988;18(1):29–36. doi: 10.1159/000215780. [DOI] [PubMed] [Google Scholar]
- Berman C. L., Yeo E. L., Wencel-Drake J. D., Furie B. C., Ginsberg M. H., Furie B. A platelet alpha granule membrane protein that is associated with the plasma membrane after activation. Characterization and subcellular localization of platelet activation-dependent granule-external membrane protein. J Clin Invest. 1986 Jul;78(1):130–137. doi: 10.1172/JCI112542. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 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]
- 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]
- 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]
- Brock T. A., Dvorak H. F., Senger D. R. Tumor-secreted vascular permeability factor increases cytosolic Ca2+ and von Willebrand factor release in human endothelial cells. Am J Pathol. 1991 Jan;138(1):213–221. [PMC free article] [PubMed] [Google Scholar]
- Chang S. Y., Chen Y. Q., Fitzgerald L. A., Honn K. V. Analysis of integrin mRNA in human and rodent tumor cells. Biochem Biophys Res Commun. 1991 Apr 15;176(1):108–113. doi: 10.1016/0006-291x(91)90896-f. [DOI] [PubMed] [Google Scholar]
- 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]
- Crissman J. D., Hatfield J. S., Menter D. G., Sloane B., Honn K. V. Morphological study of the interaction of intravascular tumor cells with endothelial cells and subendothelial matrix. Cancer Res. 1988 Jul 15;48(14):4065–4072. [PubMed] [Google Scholar]
- Dennis J. W., Laferté S., Waghorne C., Breitman M. L., Kerbel R. S. Beta 1-6 branching of Asn-linked oligosaccharides is directly associated with metastasis. Science. 1987 May 1;236(4801):582–585. doi: 10.1126/science.2953071. [DOI] [PubMed] [Google Scholar]
- Fuhrmann U., Bause E., Legler G., Ploegh H. Novel mannosidase inhibitor blocking conversion of high mannose to complex oligosaccharides. Nature. 1984 Feb 23;307(5953):755–758. doi: 10.1038/307755a0. [DOI] [PubMed] [Google Scholar]
- Fukushima K., Hirota M., Terasaki P. I., Wakisaka A., Togashi H., Chia D., Suyama N., Fukushi Y., Nudelman E., Hakomori S. Characterization of sialosylated Lewisx as a new tumor-associated antigen. Cancer Res. 1984 Nov;44(11):5279–5285. [PubMed] [Google Scholar]
- Gallatin W. M., Weissman I. L., Butcher E. C. A cell-surface molecule involved in organ-specific homing of lymphocytes. Nature. 1983 Jul 7;304(5921):30–34. doi: 10.1038/304030a0. [DOI] [PubMed] [Google Scholar]
- Gasic G. J., Gasic T. B., Stewart C. C. Antimetastatic effects associated with platelet reduction. Proc Natl Acad Sci U S A. 1968 Sep;61(1):46–52. doi: 10.1073/pnas.61.1.46. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Gasic G. J., Tuszynski G. P., Gorelik E. Interaction of the hemostatic and immune systems in the metastatic spread of tumor cells. Int Rev Exp Pathol. 1986;29:173–212. [PubMed] [Google Scholar]
- 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]
- Gilbert G. E., Drinkwater D., Barter S., Clouse S. B. Specificity of phosphatidylserine-containing membrane binding sites for factor VIII. Studies with model membranes supported by glass microspheres (lipospheres). J Biol Chem. 1992 Aug 5;267(22):15861–15868. [PubMed] [Google Scholar]
- Grossi I. M., Fitzgerald L. A., Kendall A., Taylor J. D., Sloane B. F., Honn K. V. Inhibition of human tumor cell induced platelet aggregation by antibodies to platelet glycoproteins Ib and IIb/IIIa. Proc Soc Exp Biol Med. 1987 Dec;186(3):378–383. doi: 10.3181/00379727-186-3-rc1. [DOI] [PubMed] [Google Scholar]
- Hamburger S. A., McEver R. P. GMP-140 mediates adhesion of stimulated platelets to neutrophils. Blood. 1990 Feb 1;75(3):550–554. [PubMed] [Google Scholar]
- Hamilton K. K., Sims P. J. Changes in cytosolic Ca2+ associated with von Willebrand factor release in human endothelial cells exposed to histamine. Study of microcarrier cell monolayers using the fluorescent probe indo-1. J Clin Invest. 1987 Feb;79(2):600–608. doi: 10.1172/JCI112853. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Hattori R., Hamilton K. K., McEver R. P., Sims P. J. Complement proteins C5b-9 induce secretion of high molecular weight multimers of endothelial von Willebrand factor and translocation of granule membrane protein GMP-140 to the cell surface. J Biol Chem. 1989 May 25;264(15):9053–9060. [PubMed] [Google Scholar]
- Hession C., Osborn L., Goff D., Chi-Rosso G., Vassallo C., Pasek M., Pittack C., Tizard R., Goelz S., McCarthy K. Endothelial leukocyte adhesion molecule 1: direct expression cloning and functional interactions. Proc Natl Acad Sci U S A. 1990 Mar;87(5):1673–1677. doi: 10.1073/pnas.87.5.1673. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Hoff S. D., Matsushita Y., Ota D. M., Cleary K. R., Yamori T., Hakomori S., Irimura T. Increased expression of sialyl-dimeric LeX antigen in liver metastases of human colorectal carcinoma. Cancer Res. 1989 Dec 15;49(24 Pt 1):6883–6888. [PubMed] [Google Scholar]
- 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]
- Hubbard S. C. Differential effects of oncogenic transformation on N-linked oligosaccharide processing at individual glycosylation sites of viral glycoproteins. J Biol Chem. 1987 Dec 5;262(34):16403–16411. [PubMed] [Google Scholar]
- Humphries M. J., Matsumoto K., White S. L., Olden K. Oligosaccharide modification by swainsonine treatment inhibits pulmonary colonization by B16-F10 murine melanoma cells. Proc Natl Acad Sci U S A. 1986 Mar;83(6):1752–1756. doi: 10.1073/pnas.83.6.1752. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 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]
- Karpatkin S., Pearlstein E., Ambrogio C., Coller B. S. Role of adhesive proteins in platelet tumor interaction in vitro and metastasis formation in vivo. J Clin Invest. 1988 Apr;81(4):1012–1019. doi: 10.1172/JCI113411. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Karpatkin S., Pearlstein E. Role of platelets in tumor cell metastases. Ann Intern Med. 1981 Nov;95(5):636–641. doi: 10.7326/0003-4819-95-5-636. [DOI] [PubMed] [Google Scholar]
- Kijima-Suda I., Miyazawa T., Itoh M., Toyoshima S., Osawa T. Possible mechanism of inhibition of experimental pulmonary metastasis of mouse colon adenocarcinoma 26 sublines by a sialic acid: nucleoside conjugate. Cancer Res. 1988 Jul 1;48(13):3728–3732. [PubMed] [Google Scholar]
- Kojima N., Handa K., Newman W., Hakomori S. Inhibition of selectin-dependent tumor cell adhesion to endothelial cells and platelets by blocking O-glycosylation of these cells. Biochem Biophys Res Commun. 1992 Feb 14;182(3):1288–1295. doi: 10.1016/0006-291x(92)91872-n. [DOI] [PubMed] [Google Scholar]
- 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]
- Larsen E., Palabrica T., Sajer S., Gilbert G. E., Wagner D. D., Furie B. C., Furie B. PADGEM-dependent adhesion of platelets to monocytes and neutrophils is mediated by a lineage-specific carbohydrate, LNF III (CD15). Cell. 1990 Nov 2;63(3):467–474. doi: 10.1016/0092-8674(90)90443-i. [DOI] [PubMed] [Google Scholar]
- Larsen G. R., Sako D., Ahern T. J., Shaffer M., Erban J., Sajer S. A., Gibson R. M., Wagner D. D., Furie B. C., Furie B. P-selectin and E-selectin. Distinct but overlapping leukocyte ligand specificities. J Biol Chem. 1992 Jun 5;267(16):11104–11110. [PubMed] [Google Scholar]
- Lasky L. A., Singer M. S., Yednock T. A., Dowbenko D., Fennie C., Rodriguez H., Nguyen T., Stachel S., Rosen S. D. Cloning of a lymphocyte homing receptor reveals a lectin domain. Cell. 1989 Mar 24;56(6):1045–1055. doi: 10.1016/0092-8674(89)90637-5. [DOI] [PubMed] [Google Scholar]
- Levine J. D., Harlan J. M., Harker L. A., Joseph M. L., Counts R. B. Thrombin-mediated release of factor VIII antigen from human umbilical vein endothelial cells in culture. Blood. 1982 Aug;60(2):531–534. [PubMed] [Google Scholar]
- Magnani J. L., Nilsson B., Brockhaus M., Zopf D., Steplewski Z., Koprowski H., Ginsburg V. A monoclonal antibody-defined antigen associated with gastrointestinal cancer is a ganglioside containing sialylated lacto-N-fucopentaose II. J Biol Chem. 1982 Dec 10;257(23):14365–14369. [PubMed] [Google Scholar]
- 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]
- 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]
- 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]
- Murakami H., Lam Z., Furie B. C., Reinhold V. N., Asano T., Furie B. Sulfated glycolipids are the platelet autoantigens for human platelet-binding monoclonal anti-DNA autoantibodies. J Biol Chem. 1991 Aug 15;266(23):15414–15419. [PubMed] [Google Scholar]
- Nierodzik M. L., Plotkin A., Kajumo F., Karpatkin S. Thrombin stimulates tumor-platelet adhesion in vitro and metastasis in vivo. J Clin Invest. 1991 Jan;87(1):229–236. doi: 10.1172/JCI114976. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Ogata S. I., Muramatsu T., Kobata A. New structural characteristic of the large glycopeptides from transformed cells. Nature. 1976 Feb 19;259(5544):580–582. doi: 10.1038/259580a0. [DOI] [PubMed] [Google Scholar]
- Palabrica T., Lobb R., Furie B. C., Aronovitz M., Benjamin C., Hsu Y. M., Sajer S. A., Furie B. Leukocyte accumulation promoting fibrin deposition is mediated in vivo by P-selectin on adherent platelets. Nature. 1992 Oct 29;359(6398):848–851. doi: 10.1038/359848a0. [DOI] [PubMed] [Google Scholar]
- 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]
- Ribes J. A., Francis C. W., Wagner D. D. Fibrin induces release of von Willebrand factor from endothelial cells. J Clin Invest. 1987 Jan;79(1):117–123. doi: 10.1172/JCI112771. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 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]
- Senger D. R., Galli S. J., Dvorak A. M., Perruzzi C. A., Harvey V. S., Dvorak H. F. Tumor cells secrete a vascular permeability factor that promotes accumulation of ascites fluid. Science. 1983 Feb 25;219(4587):983–985. doi: 10.1126/science.6823562. [DOI] [PubMed] [Google Scholar]
- Siegelman M. H., Weissman I. L. Human homologue of mouse lymph node homing receptor: evolutionary conservation at tandem cell interaction domains. Proc Natl Acad Sci U S A. 1989 Jul;86(14):5562–5566. doi: 10.1073/pnas.86.14.5562. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Skinner M. P., Lucas C. M., Burns G. F., Chesterman C. N., Berndt M. C. GMP-140 binding to neutrophils is inhibited by sulfated glycans. J Biol Chem. 1991 Mar 25;266(9):5371–5374. [PubMed] [Google Scholar]
- Sporn L. A., Rubin P., Marder V. J., Wagner D. D. Irradiation induces release of von Willebrand protein from endothelial cells in culture. Blood. 1984 Aug;64(2):567–570. [PubMed] [Google Scholar]
- Springer T. A. Adhesion receptors of the immune system. Nature. 1990 Aug 2;346(6283):425–434. doi: 10.1038/346425a0. [DOI] [PubMed] [Google Scholar]
- Stamper H. B., Jr, Woodruff J. J. Lymphocyte homing into lymph nodes: in vitro demonstration of the selective affinity of recirculating lymphocytes for high-endothelial venules. J Exp Med. 1976 Sep 1;144(3):828–833. doi: 10.1084/jem.144.3.828. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Steininger C. N., Eddy C. A., Leimgruber R. M., Mellors A., Welply J. K. The glycoprotease of Pasteurella haemolytica A1 eliminates binding of myeloid cells to P-selectin but not to E-selectin. Biochem Biophys Res Commun. 1992 Oct 30;188(2):760–766. doi: 10.1016/0006-291x(92)91121-6. [DOI] [PubMed] [Google Scholar]
- Stenberg P. E., McEver R. P., Shuman M. A., Jacques Y. V., Bainton D. F. A platelet alpha-granule membrane protein (GMP-140) is expressed on the plasma membrane after activation. J Cell Biol. 1985 Sep;101(3):880–886. doi: 10.1083/jcb.101.3.880. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Stoolman L. M., Rosen S. D. Possible role for cell-surface carbohydrate-binding molecules in lymphocyte recirculation. J Cell Biol. 1983 Mar;96(3):722–729. doi: 10.1083/jcb.96.3.722. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Struck D. K., Lennarz W. J. Evidence for the participation of saccharide-lipids in the synthesis of the oligosaccharide chain of ovalbumin. J Biol Chem. 1977 Feb 10;252(3):1007–1013. [PubMed] [Google Scholar]
- Tedder T. F., Isaacs C. M., Ernst T. J., Demetri G. D., Adler D. A., Disteche C. M. Isolation and chromosomal localization of cDNAs encoding a novel human lymphocyte cell surface molecule, LAM-1. Homology with the mouse lymphocyte homing receptor and other human adhesion proteins. J Exp Med. 1989 Jul 1;170(1):123–133. doi: 10.1084/jem.170.1.123. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Tulsiani D. R., Harris T. M., Touster O. Swainsonine inhibits the biosynthesis of complex glycoproteins by inhibition of Golgi mannosidase II. J Biol Chem. 1982 Jul 25;257(14):7936–7939. [PubMed] [Google Scholar]
- Wagner D. D., Ivatt R., Destree A. T., Hynes R. O. Similarities and differences between the fibronectins of normal and transformed hamster cells. J Biol Chem. 1981 Nov 25;256(22):11708–11715. [PubMed] [Google Scholar]
- Wagner D. D., Lawrence S. O., Ohlsson-Wilhelm B. M., Fay P. J., Marder V. J. Topology and order of formation of interchain disulfide bonds in von Willebrand factor. Blood. 1987 Jan;69(1):27–32. [PubMed] [Google Scholar]
- Wagner D. D., Olmsted J. B., Marder V. J. Immunolocalization of von Willebrand protein in Weibel-Palade bodies of human endothelial cells. J Cell Biol. 1982 Oct;95(1):355–360. doi: 10.1083/jcb.95.1.355. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Yousefi S., Higgins E., Daoling Z., Pollex-Krüger A., Hindsgaul O., Dennis J. W. Increased UDP-GlcNAc:Gal beta 1-3GaLNAc-R (GlcNAc to GaLNAc) beta-1, 6-N-acetylglucosaminyltransferase activity in metastatic murine tumor cell lines. Control of polylactosamine synthesis. J Biol Chem. 1991 Jan 25;266(3):1772–1782. [PubMed] [Google Scholar]
- Zhou Q., Moore K. L., Smith D. F., Varki A., McEver R. P., Cummings R. D. The selectin GMP-140 binds to sialylated, fucosylated lactosaminoglycans on both myeloid and nonmyeloid cells. J Cell Biol. 1991 Oct;115(2):557–564. doi: 10.1083/jcb.115.2.557. [DOI] [PMC free article] [PubMed] [Google Scholar]