Skip to main content
Log in

Characterization of deoxyguanosine-resistant hypoxanthine-guanine phosphoribosyltransferase metastatic variants altered in soybean-agglutinin-binding properties and cell-surface glycoproteins

  • Original Papers
  • Experimental Oncology
  • Published:
Journal of Cancer Research and Clinical Oncology Aims and scope Submit manuscript

Summary

The isolation of deoxyguanosine-resistant 10T 1/2 mouse cell lines following stepwise selection in the presence of increasing concentrations of drug led to the identification of a highly metastatic line, as measured by the ability to form secondary tumors in syngenic mice after intravenous injection. This metastatic deoxyguanosine-resistant mutant was determined to be deficient in hypoxanthine-guanine phosphoribosyltransferase activity, accounting for the resistance to deoxyguanosine. Lectin-binding studies determined that the metastatic potential of high- and low-metastatic revertant clones of this deoxyguanosine-resistant mutant was negatively correlated to soybean agglutinin binding, but not to concanavalin A or wheat germ agglutinin binding. Examination of labelled cell-surface glycoproteins led to the identification of two glycoproteins, gp80 and gp48, which were present on the low-metastatic wild-type cell line but absent from the highly metastatic drug-resistant cells. Our studies suggest that these cell-surface glycoprotein alterations play a role in determining the malignant properties of the cells, and indicate that metastatic variants with the properties described in this report would be useful biological tools for investigations into the roles played by specific cell-surface structures in mechanisms of tumor progression.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Similar content being viewed by others

Abbreviations

HGPRT:

hypoxanthine-guanine phosphoribosyltransferase

WGA:

wheat germ agglutinin

SBA:

soybean agglutinin

References

  • Aldaheff JA (1989) Malignant cell glycoproteins and glycolipids. Crit Rev Oncol Hematol 9:37–107

    Google Scholar 

  • Altevogt P, Fogel M, Cheingsong-Popov R, Dennis J, Robinson P, Schirrmacher V (1983) Different patterns of lectin binding and cell surface sialylation detected in high- and low-metastatic tumor lines. Cancer Res 43:5138–5144

    Google Scholar 

  • Barnett SC, Eccles SA (1984) Studies of mammary carcinoma metastasis in a mouse model system: II. Lectin binding properties of cells in relation to the incidence and organ distribution of metastasis. Clin Exp Metastasis 2:297–310

    Google Scholar 

  • Blin N, Stafford DW (1976) A general method for isolation of high molecular DNA from eukaryotes. Nucleic Acid Res 3:2303–2308

    Google Scholar 

  • Blosmanis R, Wright JA, Goldenberg GJ (1987) Sensitivity to melphalan as a function of transport activity and proliferative rate in BALB/c 3T3 fibroblasts. Cancer Res 47:1273–1277

    Google Scholar 

  • Buckley ND, Carlsen SA (1988) Involvement of Soybean agglutinin binding cells in the lymphatic metastasis of the R3230AC rat mammary adenocarcinoma. Cancer Res 48:1451–1455

    Google Scholar 

  • Collard JG, Schijven JF, Bikker A, LaRiviere G, Bolscher JGM, Roos E (1986) Cell surface sialic acid and the invasive and metastatic potential of T cell hybridomas. Cancer Res 46:3521–3527

    Google Scholar 

  • Dennis JW, Laferte S (1987) Tumor cell surface carbohydrate and the metastatic phenotype. Cancer Metastatic Rev 5:185–204

    Google Scholar 

  • Egan SE, McClarty GA, Jarolim L, Wright JA, Spiro I, Hager G, Greenberg AH (1987) Expression of H-ras correlates with the metastatic potential: Evidence for direct regulation of the metastatic phenotype in 10T1/2 and NIH3T3 cells. Mol Cell Biol 7:830–837

    Google Scholar 

  • Feinberg AP, Vogelstein B (1983) A technique for radiolabeling DNA restriction endonuclease fragments to high specific activity. Anal Biochem 132:6–13

    Google Scholar 

  • Gough NM (1988) Rapid and quantitative preparation of cytoplasmic RNA from small numbers of cells. Anal Biochem 173:93–95

    Google Scholar 

  • Greenberg AH, Egan SE, Jarolim L, Gingras MC, Wright JA (1987) Natural killer cell regulation of implantation and early lung growth of H-ras-transformed 10T1/2 fibroblasts in mice. Cancer Res 47:4801–4805

    Google Scholar 

  • Greenberg AH, Egan SE, Wright JA (1989) Oncogenes and metastatic progression. Invasion Metastases 9:360–378

    Google Scholar 

  • Gudas LJ, Ullman B, Cohen A, Martin DW Jr (1978) Deoxyguanosine toxicity in a mouse T lymphoma: relationship to purine nucleoside phosphorylase-associated immune dysfunction. Cell 14:531

    Google Scholar 

  • Hards RG, Wright JA (1981)N-carbamoyloxyurea-resistant Chinese hamster ovary cells with elevated levels of ribonucleotide reductase activity. J Cell Physiol 106:309–319

    Google Scholar 

  • Kerbel RS, Dennis JW, Lagarde AE, Frost P (1982) Tumor progression and metastasis: an experimental approach using lectin resistant tumor variants. Cancer Metastasis Rev 1:99–140

    Google Scholar 

  • Laferte S, Dennis JW (1988) Glycosylation-dependent Collagenbinding activities of two membrane glycoproteins in MDAY-D2 tumor cells. Cancer Res 48:4743–4748

    Google Scholar 

  • Lang E, Schirrmacher V, Altevogt P (1988) Molecular identification of lectin binding sites differentiating related low and high metastatic murine lymphomas. Clin Exp Metastasis 6:61–72

    Google Scholar 

  • Ledbetter JA, Seaman WE, Tsu TT, Herzenberg LA (1981) Lyt-2 and Lyt-3 antigens are on two different polypeptide subunits linked by disulfide bonds. J Exp Med 153:1503–1516

    Google Scholar 

  • Liotta LA (1986) Tumor invasion and metastasis — role of the extracellular matrix: Rhoads Memorial Award Lecture. Cancer Res 46:1–7

    Google Scholar 

  • McClarty GA, Chan A, Engstrom Y, Wright JA, Thelander L (1987) Elevated expression of M1 and M2 components and drug-induced posttranscriptional modulation of ribonucleotide reductase in a hydroxyurea-resistant mouse cell line. Biochemistry 26:8004–8011

    Google Scholar 

  • Nabi IR, Raz A (1987) Cell shape modulation alters glycosylation of metastatic melanoma cell surface antigen. Int J Cancer 40:396–402

    Google Scholar 

  • Nanden D, Ball EH, Sanwal BD (1990) Two proteins of the endoplasmic reticulum bind denatured collagen. Biochem Cell Biol 68:1057–1061

    Google Scholar 

  • Nicander B, Reichard P (1985) Relations between synthesis of deoxyribonucleotide and DNA replication in 3T6 fibroblasts. J Biol Chem 260:5376–5381

    Google Scholar 

  • Parfett CLJ, Jamieson JC, Wright JA (1983) Changes in cell surface glycoproteins on non-differentiating L6 rat myoblasts selected for resistance to concanavalin A. Exp Cell Res 144:405–415

    Google Scholar 

  • Penno MB, Passaniti A, Fridman R, Hart GW, Jordan C, Kumar S, Scott AF (1989)In vitro galactosylation of a 110-kDa glycoprotein by an endogenous cell surface galactosyltransferase correlates with the invasiveness of adrenal carcinoma cells. Proc Natl Acad Sci USA 86:6057–6061

    Google Scholar 

  • Poste G (1982) Experimental systems for analysis of the malignant phenotype. Cancer Metastasis Rev 1:141–201

    Google Scholar 

  • Sidi Y, Mitchell BS (1984) 2-Deoxyguanosine toxicity for B and mature T lymphoid cell lines is mediated by guanine ribonucleotide accumulation. J Clin Invest 74:1640

    Google Scholar 

  • Spearman MA, Jamieson JC, Wright JA (1987) Studies on the effect of glycoprotein processing inhibitors on fusion of L6 myoblast cell lines. Exp Cell Res 168:116–126

    Google Scholar 

  • Tanner JM, Anstee DJ (1976) A method for the direct demonstration of the lectin-binding components of the human erythrocyte membrane. Biochem J 153:265–270

    Google Scholar 

  • Ullman B (1989) Adenosine, deoxyadenosine and deoxyguanosine. In: Gupta RS (ed) Drug resistance in mammalian cells: vol 1. Antimetabolic and cytotoxic analogs. CRC Press, Boca Raton, pp 69–88

    Google Scholar 

  • Ullman BG, Martin DW Jr (1984) Specific cytotoxicity of arabinosylguanine toward cultured T lymphoblasts. J Clin Invest 74:951

    Google Scholar 

  • Ullman BG, Gudas LJ, Clift SM, Martin DW Jr (1979) Isolation and characterization of purine-nucleoside phosphorylase-deficient T-lymphoma cells and secondary mutants with altered ribonucleotide reductase: genetic model for immunodeficiency disease. Proc Natl Acad Sci USA 76:1074

    Google Scholar 

  • Wright JA (1989) Altered mammalian ribonucleoside diphosphate reductase from mutant cell lines. Int Encycl Pharmacol Ther 128:89–111

    Google Scholar 

  • Wright JA, Alam TG, McClarty GA, Tagger AY, Thelander L (1987) Altered expression of ribonucleotide reductase and role of M2 gene amplification in hydroxyurea-resistant hamster, mouse, rat and human cell lines. Somatic Cell Mol Genet 13:155–165

    Google Scholar 

  • Wright JA, Hards RG, Dick JE (1981) Studies of mammalian ribonucleotide reductase activity in intact permeabilized cells: a genetic approach. Adv Enzyme Regul 19:105–127

    Google Scholar 

  • Wright JA, Egan SE, Greenberg AH (1990) Genetic regulation of metastatic progression. Anticancer Res 10:1247–1256

    Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Rights and permissions

Reprints and permissions

About this article

Cite this article

Damen, J.E., Spearman, M.A., Greenberg, A.H. et al. Characterization of deoxyguanosine-resistant hypoxanthine-guanine phosphoribosyltransferase metastatic variants altered in soybean-agglutinin-binding properties and cell-surface glycoproteins. J Cancer Res Clin Oncol 117, 305–312 (1991). https://doi.org/10.1007/BF01630712

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF01630712

Key words

Navigation