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. 1990 Aug 1;111(2):773–781. doi: 10.1083/jcb.111.2.773

Tumor cell surface beta 1-4-linked galactose binds to lectin(s) on microvascular endothelial cells and contributes to organ colonization

PMCID: PMC2116217  PMID: 2116422

Abstract

Cell surface carbohydrate structures acting as ligands for tissue specific mammalian lectins have been implicated in cell-cell interactions during embryogenesis, lymphocyte homing, and tumor cell metastasis. In this report, we provide evidence that beta 1-4 linked galactose (Gal) residues in N-linked oligosaccharides on the surface of blood born tumor cells serve as a ligand for binding to microvascular endothelial cells. D36W25, a class 1 glycosylation mutant of the MDAY- D2 lymphoreticular tumor cell line, lacks sialic acid and Gal in cellular glycans due to a defect in the Golgi UDP-Gal transporter. Using UDP-Gal and bovine galactosyltransferase in vitro, beta 1-4 Gal was restored to the surface of the cells and 70% of the galactosylated glycans persisted for 8 h in vitro at 37 degrees C. Compared to mock- treated D36W25 cells, galactosylated D36W25 cells showed an 80% increase in binding to microvascular endothelial cell monolayers in vitro. The enhanced binding of galactosylated D36W25 cells to endothelial cell was inhibited by the addition of lactosamine- conjugated albumin to the assay. Consistent with these observations, swainsonine and castinospermine, two inhibitors of N-linked processing that result in loss of lactosamine antennae inhibited the binding of wild-type MDAY-D2 cells to endothelial cells in vitro. Injection of radiolabeled tumor cells into the circulation of syngeneic mice, showed that galactosylation of D36W25 cells resulted in 2-3 more tumor cells retained in the lungs and livers. In addition, galactosylation of D36W25 cells increased by 30-fold the number of visible liver metastases on inspection 4 wk after tumor cell injection. These results suggest that beta 1-4Gal-binding lectins on microvascular endothelial cells can contribute to retention and secondary tumor formation of blood born tumor cells. With the increasing availability of purified glycosyltransferases, reconstruction of a variety of carbohydrate sequences on the surface of class 1 mutants provides a controlled means of studying carbohydrate-lectin interactions on viable cells.

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Selected References

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  1. Aizawa S., Tavassoli M. Molecular basis of the recognition of intravenously transplanted hemopoietic cells by bone marrow. Proc Natl Acad Sci U S A. 1988 May;85(9):3180–3183. doi: 10.1073/pnas.85.9.3180. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Alby L., Auerbach R. Differential adhesion of tumor cells to capillary endothelial cells in vitro. Proc Natl Acad Sci U S A. 1984 Sep;81(18):5739–5743. doi: 10.1073/pnas.81.18.5739. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Ashwell G., Harford J. Carbohydrate-specific receptors of the liver. Annu Rev Biochem. 1982;51:531–554. doi: 10.1146/annurev.bi.51.070182.002531. [DOI] [PubMed] [Google Scholar]
  4. Belardelli F., Ferrantini M., Maury C., Santurbano L., Gresser I. Biologic and biochemical differences between in vitro and in vivo passaged Friend erythroleukemia cells. I. Tumorigenicity and capacity to metastasize. Int J Cancer. 1984 Sep 15;34(3):389–395. doi: 10.1002/ijc.2910340316. [DOI] [PubMed] [Google Scholar]
  5. Beuth J., Ko H. L., Oette K., Pulverer G., Roszkowski K., Uhlenbruck G. Inhibition of liver metastasis in mice by blocking hepatocyte lectins with arabinogalactan infusions and D-galactose. J Cancer Res Clin Oncol. 1987;113(1):51–55. doi: 10.1007/BF00389966. [DOI] [PubMed] [Google Scholar]
  6. 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]
  7. Brew K., Vanaman T. C., Hill R. L. The role of alpha-lactalbumin and the A protein in lactose synthetase: a unique mechanism for the control of a biological reaction. Proc Natl Acad Sci U S A. 1968 Feb;59(2):491–497. doi: 10.1073/pnas.59.2.491. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Castronovo V., Colin C., Parent B., Foidart J. M., Lambotte R., Mahieu P. Possible role of human natural anti-Gal antibodies in the natural antitumor defense system. J Natl Cancer Inst. 1989 Feb 1;81(3):212–216. doi: 10.1093/jnci/81.3.212. [DOI] [PubMed] [Google Scholar]
  9. Crissman J. D., Hatfield J., Schaldenbrand M., Sloane B. F., Honn K. V. Arrest and extravasation of B16 amelanotic melanoma in murine lungs. A light and electron microscopic study. Lab Invest. 1985 Oct;53(4):470–478. [PubMed] [Google Scholar]
  10. Cummings R. D., Kornfeld S. Characterization of the structural determinants required for the high affinity interaction of asparagine-linked oligosaccharides with immobilized Phaseolus vulgaris leukoagglutinating and erythroagglutinating lectins. J Biol Chem. 1982 Oct 10;257(19):11230–11234. [PubMed] [Google Scholar]
  11. Dennis J. W. Different metastatic phenotypes in two genetic classes of wheat germ agglutinin-resistant tumor cell mutants. Cancer Res. 1986 Sep;46(9):4594–4600. [PubMed] [Google Scholar]
  12. Dennis J. W. Effects of swainsonine and polyinosinic:polycytidylic acid on murine tumor cell growth and metastasis. Cancer Res. 1986 Oct;46(10):5131–5136. [PubMed] [Google Scholar]
  13. Dennis J. W., Laferté S., Fukuda M., Dell A., Carver J. P. Asn-linked oligosaccharides in lectin-resistant tumor-cell mutants with varying metastatic potential. Eur J Biochem. 1986 Dec 1;161(2):359–373. doi: 10.1111/j.1432-1033.1986.tb10455.x. [DOI] [PubMed] [Google Scholar]
  14. 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]
  15. Dennis J. W., Laferté S., Yagel S., Breitman M. L. Asparagine-linked oligosaccharides associated with metastatic cancer. Cancer Cells. 1989 Nov;1(3):87–92. [PubMed] [Google Scholar]
  16. Drickamer K. Two distinct classes of carbohydrate-recognition domains in animal lectins. J Biol Chem. 1988 Jul 15;263(20):9557–9560. [PubMed] [Google Scholar]
  17. Elbein A. D. Inhibitors of the biosynthesis and processing of N-linked oligosaccharide chains. Annu Rev Biochem. 1987;56:497–534. doi: 10.1146/annurev.bi.56.070187.002433. [DOI] [PubMed] [Google Scholar]
  18. Elbein A. D., Szumilo T., Sanford B. A., Sharpless K. B., Adams C. Effect of isomers of swainsonine on glycosidase activity and glycoprotein processing. Biochemistry. 1987 May 5;26(9):2502–2510. doi: 10.1021/bi00383a015. [DOI] [PubMed] [Google Scholar]
  19. Gallatin M., St John T. P., Siegelman M., Reichert R., Butcher E. C., Weissman I. L. Lymphocyte homing receptors. Cell. 1986 Mar 14;44(5):673–680. doi: 10.1016/0092-8674(86)90832-9. [DOI] [PubMed] [Google Scholar]
  20. Gartner T. K., Williams D. C., Minion F. C., Phillips D. R. Thrombin-induced platelet aggregation is mediated by a platelet plasma membrane-bound lectin. Science. 1978 Jun 16;200(4347):1281–1283. doi: 10.1126/science.663608. [DOI] [PubMed] [Google Scholar]
  21. Hakomori S., Kannagi R. Glycosphingolipids as tumor-associated and differentiation markers. J Natl Cancer Inst. 1983 Aug;71(2):231–251. [PubMed] [Google Scholar]
  22. Hart I. R., Fidler I. J. Role of organ selectivity in the determination of metastatic patterns of B16 melanoma. Cancer Res. 1980 Jul;40(7):2281–2287. [PubMed] [Google Scholar]
  23. Higa H. H., Paulson J. C. Sialylation of glycoprotein oligosaccharides with N-acetyl-, N-glycolyl-, and N-O-diacetylneuraminic acids. J Biol Chem. 1985 Jul 25;260(15):8838–8849. [PubMed] [Google Scholar]
  24. Hinek A., Wrenn D. S., Mecham R. P., Barondes S. H. The elastin receptor: a galactoside-binding protein. Science. 1988 Mar 25;239(4847):1539–1541. doi: 10.1126/science.2832941. [DOI] [PubMed] [Google Scholar]
  25. 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]
  26. Ishikawa M., Dennis J. W., Man S., Kerbel R. S. Isolation and characterization of spontaneous wheat germ agglutinin-resistant human melanoma mutants displaying remarkably different metastatic profiles in nude mice. Cancer Res. 1988 Feb 1;48(3):665–670. [PubMed] [Google Scholar]
  27. 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]
  28. Kataoka M., Tavassoli M. Identification of lectin-like substances recognizing galactosyl residues of glycoconjugates on the plasma membrane of marrow sinus endothelium. Blood. 1985 May;65(5):1163–1171. [PubMed] [Google Scholar]
  29. Kerbel R. S., Florian M., Man M. S., Dennis J., McKenzie I. F. Carcinogenicity of tumor cell populations: origin of a putative H-2 isoantigenic loss variant tumor. J Natl Cancer Inst. 1980 May;64(5):1221–1230. [PubMed] [Google Scholar]
  30. Laemmli U. K. Cleavage of structural proteins during the assembly of the head of bacteriophage T4. Nature. 1970 Aug 15;227(5259):680–685. doi: 10.1038/227680a0. [DOI] [PubMed] [Google Scholar]
  31. Laferté S., Dennis J. W. Glycosylation-dependent collagen-binding activities of two membrane glycoproteins in MDAY-D2 tumor cells. Cancer Res. 1988 Sep 1;48(17):4743–4748. [PubMed] [Google Scholar]
  32. Laferté S., Fukuda M. N., Fukuda M., Dell A., Dennis J. W. Glycosphingolipids of lectin-resistant mutants of the highly metastatic mouse tumor cell line, MDAY-D2. Cancer Res. 1987 Jan 1;47(1):150–159. [PubMed] [Google Scholar]
  33. Lagarde A. E., Donaghue T. P., Kerbel R., Siminovitch L. Metastatic properties of distinct phenotypic classes of lectin-resistant mutants isolated from murine MDAY-D2 cell line. Somat Cell Mol Genet. 1984 Sep;10(5):503–519. doi: 10.1007/BF01534855. [DOI] [PubMed] [Google Scholar]
  34. Merkle R. K., Cummings R. D. Asparagine-linked oligosaccharides containing poly-N-acetyllactosamine chains are preferentially bound by immobilized calf heart agglutinin. J Biol Chem. 1988 Nov 5;263(31):16143–16149. [PubMed] [Google Scholar]
  35. Nicolson G. L. Organ specificity of tumor metastasis: role of preferential adhesion, invasion and growth of malignant cells at specific secondary sites. Cancer Metastasis Rev. 1988 Jun;7(2):143–188. doi: 10.1007/BF00046483. [DOI] [PubMed] [Google Scholar]
  36. Parish C. R., Rylatt D. B., Snowden J. M. Demonstration of lymphocyte surface lectins that recognize sulphated polysaccharides. J Cell Sci. 1984 Apr;67:145–158. doi: 10.1242/jcs.67.1.145. [DOI] [PubMed] [Google Scholar]
  37. Paulson J. C., Sadler J. E., Hill R. L. Restoration of specific myxovirus receptors to asialoerythrocytes by incorporation of sialic acid with pure sialyltransferases. J Biol Chem. 1979 Mar 25;254(6):2120–2124. [PubMed] [Google Scholar]
  38. Raz A., Lotan R. Endogenous galactoside-binding lectins: a new class of functional tumor cell surface molecules related to metastasis. Cancer Metastasis Rev. 1987;6(3):433–452. doi: 10.1007/BF00144274. [DOI] [PubMed] [Google Scholar]
  39. Schaaf-Lafontaine N., Hooghe R. J., Vander Plaetse F. Modification of blood-borne arrest properties of lymphoma cells by inhibitors of protein glycosylation suggests the existence of endogenous lectins. Carbohydr Res. 1985 May 15;138(2):315–323. doi: 10.1016/0008-6215(85)85114-4. [DOI] [PubMed] [Google Scholar]
  40. Schirrmacher V., Cheingsong-Popov R., Arnheiter H. Hepatocyte-tumor cell interaction in vitro. I. Conditions for rosette formation and inhibition by anti-H-2 antibody. J Exp Med. 1980 Apr 1;151(4):984–989. doi: 10.1084/jem.151.4.984. [DOI] [PMC free article] [PubMed] [Google Scholar]
  41. Schirrmacher V., Shantz G., Clauer K., Komitowski D., Zimmermann H. P., Lohmann-Matthes M. L. Tumor metastases and cell-mediated immunity in a model system in DBA/2 mice. I. Tumor invasiveness in vitro and metastasis formation in vivo. Int J Cancer. 1979 Feb;23(2):233–244. doi: 10.1002/ijc.2910230215. [DOI] [PubMed] [Google Scholar]
  42. Schlepper-Schäfer J., Kolb-Bachofen V., Kolb H. Analysis of lectin-dependent recognition of desialylated erythrocytes by Kupffer cells. Biochem J. 1980 Mar 15;186(3):827–831. doi: 10.1042/bj1860827. [DOI] [PMC free article] [PubMed] [Google Scholar]
  43. Sparrow C. P., Leffler H., Barondes S. H. Multiple soluble beta-galactoside-binding lectins from human lung. J Biol Chem. 1987 May 25;262(15):7383–7390. [PubMed] [Google Scholar]
  44. Stoolman L. M., Tenforde T. S., Rosen S. D. Phosphomannosyl receptors may participate in the adhesive interaction between lymphocytes and high endothelial venules. J Cell Biol. 1984 Oct;99(4 Pt 1):1535–1540. doi: 10.1083/jcb.99.4.1535. [DOI] [PMC free article] [PubMed] [Google Scholar]
  45. Tao T. W., Johnson L. K. Altered adhesiveness of tumor cell surface variants with reduced metastasizing capacity--reduced adhesiveness to vascular wall components in culture. Int J Cancer. 1982 Dec 15;30(6):763–766. doi: 10.1002/ijc.2910300614. [DOI] [PubMed] [Google Scholar]
  46. Torres C. R., Hart G. W. Topography and polypeptide distribution of terminal N-acetylglucosamine residues on the surfaces of intact lymphocytes. Evidence for O-linked GlcNAc. J Biol Chem. 1984 Mar 10;259(5):3308–3317. [PubMed] [Google Scholar]
  47. Yagel S., Feinmesser R., Waghorne C., Lala P. K., Breitman M. L., Dennis J. W. Evidence that beta 1-6 branched Asn-linked oligosaccharides on metastatic tumor cells facilitate invasion of basement membranes. Int J Cancer. 1989 Oct 15;44(4):685–690. doi: 10.1002/ijc.2910440422. [DOI] [PubMed] [Google Scholar]

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