Skip to main content
Log in

Towards functional glycomics by localization of binding sites for tissue lectins: lectin histochemical reactivity for galectins during diethylstilbestrol-induced kidney tumorigenesis in male Syrian hamster

  • Original paper
  • Published:
Histochemistry and Cell Biology Aims and scope Submit manuscript

Abstract

Endogenous lectins act as effectors of cellular activities such as growth regulation, migration, and adhesion. Following their immunohistochemical localization in our previous study (Saussez et al. in Histochem Cell Biol 123:29–41, 2005) we purified several galectins and used them as tools for monitoring accessible binding sites. Herein, we report the use of galectin histochemistry for the analysis of diethylstilbestrol (DES)-induced renal tumors in male Syrian hamster kidney (SHKT). Sections of normal kidney and DES-treated kidney were analyzed with biotinylated galectins-1, -3 (full-length and truncated), and -7. Accessible binding sites were detected, localization was predominantly extracellular and confined to medium-sized and large tumors. Monitoring the SHKT-derived HKT-1097 line, processed in vitro or as xenograft material, cytoplasmic and nuclear staining for galectins-1, -3, and -3tr could be observed. Adaptation of SHKT cells to long-term growth in culture is thus associated with emergence of this signal. Our data set illustrates the feasibility to complement immunohistochemical data by application of the tissue lectins as probes, and to detect regulation of galectin reactivity with differential characteristics within tumor progression in vivo and unique features of the tumor cell line in vitro and in vivo.

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.

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5

Similar content being viewed by others

Abbreviations

BC:

Bowman’s capsule

DES:

Diethylstilbestrol

DMEM:

Dulbecco’s modified Eagle medium

DPBS:

Dulbecco’s PBS

ECM:

Extracellular matrix

FBS:

Fetal bovine serum

ISOM:

Inner stripe of the outer medulla

LI:

Labeling index

LT:

Large tumor

MOD:

Mean optical density

MT:

Medium-sized tumor

NGS:

Normal goat serum

OSOM:

Outer stripe of the outer medulla

PAF:

Paraformaldehyde

PAS:

Periodic acid-Schiff

PTAV:

Perivascular tissue surrounding arcuate artery and vein

RCC:

Renal cell carcinoma

s.c.:

Subcutaneous

SHKT:

Syrian hamster kidney tumor

TB:

Tumorous buds

References

  • Agrwal N, Sun Q, Wang SY, Wang JL (1993) Carbohydrate-binding protein 35. I. Properties of the recombinant polypeptide and the individuality of the domains. J Biol Chem 268:14932–14939

    PubMed  CAS  Google Scholar 

  • Ahmad N, Gabius HJ, André S, Kaltner H, Sabesan S, Roy R, Liu B, Macaluso F, Brewer CF (2004) Galectin-3 precipitates as a pentamer with synthetic multivalent carbohydrates and forms heterogeneous cross-linked complexes. J Biol Chem 279:10841–10847

    Article  PubMed  CAS  Google Scholar 

  • André S, Kojima S, Yamazaki N, Fink C, Kaltner H, Kayser K, Gabius HJ (1999) Galectins-1 and -3 and their ligands in tumor biology. J Cancer Res Clin Oncol 125:461–474

    Article  PubMed  Google Scholar 

  • André S, Unverzagt C, Kojima S, Frank M, Seifert J, Fink C, Kayser K, von der Lieth CW, Gabius HJ (2004a) Determination of modulation of ligand properties of synthetic complex-type biantennary N-glycans by introduction of bisecting GlcNAc in silico, in vitro and in vivo. Eur J Biochem 271:118–134

    Article  CAS  Google Scholar 

  • André S, Kaltner H, Furuike T, Nishimura SI, Gabius HJ (2004b) Persubstituted cyclodextrin-based glycoclusters as inhibitors of protein–carbohydrate recognition using purified plant and mammalian lectins and wild-type and lectin-gene-transfected tumor cells as targets. Bioconjug Chem 15:87–98

    Article  CAS  Google Scholar 

  • André S, Kaltner H, Lensch M, Russwurm R, Siebert HC, Fallsehr C, Tajkhorshid E, Heck AJR, von Knebel Doeberitz M, Gabius HJ, Kopitz J (2005a) Determination of structural and functional overlap/divergence of five proto-type galectins by analysis of the growth-regulatory interaction with ganglioside GM1 in silico and in vitro on human neuroblastoma cells. Int J Cancer 114:46–57

    Article  CAS  Google Scholar 

  • André S, Arnusch CJ, Kuwabara I, Russwurm R, Kaltner H, Gabius HJ, Pieters RJ (2005b) Identification of peptide ligands for malignancy- and growth-regulating galectins using random phage-display and designed combinatorial peptide libraries. Bioorg Med Chem 13:563–573

    Article  CAS  Google Scholar 

  • Bao Q, Hughes RC (1999) Galectin-3 and polarized growth within collagen gels of wild-type and ricin-resistant MDCK renal epithelial cells. Glycobiology 9:489–495

    Article  PubMed  CAS  Google Scholar 

  • Bhat HK, Hacker HJ, Bannasch B, Thompson EA, Liehr JG (1995) Differential regulation by estrogen of c-fos in hamster kidney and estrogen-induced kidney tumor. Int J Oncol 7:527–534

    CAS  Google Scholar 

  • Brockhausen I, Schutzbach J, Kuhns W (1998) Glycoproteins and their relationship to human disease. Acta Anat (Basel) 161:36–78

    Article  CAS  Google Scholar 

  • Brown DF, Dababo MA, Hladik CL, Eagan KP, White CL III, Rushing EJ (1998) Hormone receptor immunoreactivity in hemangioblastomas and clear cell renal cell carcinomas. Mod Pathol 11:55–59

    PubMed  CAS  Google Scholar 

  • Bullock SL, Johnson TM, Bao Q, Hughes RC, Winyard PJ, Woolf AS (2001) Galectin-3 modulates ureteric bud branching in organ culture of the developing mouse kidney. J Am Soc Nephrol 12:515–523

    PubMed  CAS  Google Scholar 

  • Camby I, Belot N, Lefranc F, Sadeghi N, de Launoit Y, Kaltner H, Musette S, Darro F, Danguy A, Salmon I, Gabius HJ, Kiss R (2002) Galectin-1 modulates human glioblastoma cell migration into the brain through modifications to the actin cytoskeleton and levels of expression of small GTPases. J Neuropathol Exp Neurol 61:585–596

    PubMed  CAS  Google Scholar 

  • Caselitz J (1987) Lectins and blood group substances as “tumor markers”. Curr Top Pathol 77:245–277

    PubMed  CAS  Google Scholar 

  • Choe YS, Shim C, Choi D, Sang Lee C, Lee KK, Kim K (1997) Expression of galectin-1 mRNA in the mouse uterus is under the control of ovarian steroids during blastocyst implantation. Mol Reprod Dev 48:261–266

    Article  PubMed  CAS  Google Scholar 

  • Clerch LB, Whitney PL, Massaro D (1987) Rat lung lectin synthesis, degradation and activation. Developmental regulation and modulation by dexamethasone. Biochem J 245:683–690

    PubMed  CAS  Google Scholar 

  • Delbrouck C, Doyen I, Belot N, Decaestecker C, Ghanooni R, de Lavareille A, Kaltner H, Choufani G, Danguy A, Vandenhoven G, Gabius HJ, Hassid S, Kiss R (2002) Galectin-1 is overexpressed in nasal polyps under budesonide and inhibits eosinophil migration. Lab Invest 82:147–158

    PubMed  CAS  Google Scholar 

  • Di Silverio F, Sciarra A, Flammia GP, Mariani M, De Vico A (1997) Multiple primary tumors: 17 cases of renal-cell carcinoma associated with primary tumors involving different steroid-hormone target tissues. World J Urol 15:203–209

    Article  PubMed  CAS  Google Scholar 

  • Foddy L, Stamatoglou SC, Hughes RC (1990) An endogenous carbohydrate-binding protein of baby hamster kidney (BHK21 C13) cells. Temporal changes in cellular expression in the developing kidney. J Cell Sci 97:139–148

    PubMed  CAS  Google Scholar 

  • Francois C, van Velthoven R, De Lathouwer O, Moreno C, Peltier A, Kaltner H, Salmon I, Gabius HJ, Danguy A, Decaestecker C, Kiss R (1999) Galectin-1 and galectin-3 binding pattern expression in renal cell carcinomas. Am J Clin Pathol 112:194–203

    PubMed  CAS  Google Scholar 

  • Gabius HJ (1990) Influence of type of linkage and spacer on the interaction of β-galactoside-binding proteins with immobilized affinity ligands. Anal Biochem 189:91–94

    Article  PubMed  CAS  Google Scholar 

  • Gabius HJ (2001) Glycohistochemistry: the why and how of detection and localization of endogenous lectins. Anat Histol Embryol 30:3–31

    Article  PubMed  CAS  Google Scholar 

  • Gabius HJ, Wosgien B, Hendrys M, Bardosi A (1991) Lectin localization in human nerve by biochemically defined lectin-binding glycoproteins, neoglycoprotein and lectin-specific antibody. Histochemistry 95:269–277

    Article  PubMed  CAS  Google Scholar 

  • Gabius HJ, Siebert HC, André S, Jiménez-Barbero J, Rüdiger H (2004) Chemical biology of the sugar code. ChemBioChem 5:740–764

    Article  PubMed  CAS  Google Scholar 

  • Gitt MA, Barondes SH (1991) Genomic sequence and organization of two members of a human lectin gene family. Biochemistry 30:82–89

    Article  PubMed  CAS  Google Scholar 

  • Goldstone SD, Lavin MF (1991) Isolation of a cDNA clone, encoding a human β-galactoside binding protein, overexpressed during glucocorticoid-induced cell death. Biochem Biophys Res Commun 178:746–750

    Article  PubMed  CAS  Google Scholar 

  • Hakomori S (1998) Cancer-associated glycosphingolipid antigens: their structure, organization, and function. Acta Anat (Basel) 161:79–90

    Article  CAS  Google Scholar 

  • Hou X, Li JJ, Chen W, Li SA (1996) Estrogen-induced proto-oncogene and suppressor gene expression in the hamster kidney: significance for estrogen carcinogenesis. Cancer Res 56:2616–2620

    PubMed  CAS  Google Scholar 

  • Kopitz J, André S, von Reitzenstein C, Versluis K, Kaltner H, Pieters RJ, Wasano K, Kuwabara I, Liu FT, Cantz M, Heck AJR, Gabius HJ (2003) Homodimeric galectin-7 (p53-induced gene 1) is a negative growth regulator for human neuroblastoma cells. Oncogene 22:6277–6288

    Article  PubMed  CAS  Google Scholar 

  • Kriz W, Bankir L (1988) A standard nomenclature for structures of the kidney. The Renal Commission of the International Union of Physiological Sciences (IUPS). Kidney Int 33:1–7

    Article  PubMed  CAS  Google Scholar 

  • Langner C, Ratschek M, Rehak P, Schips L, Zigeuner R (2004) Steroid hormone receptor expression in renal cell carcinoma: an immunohistochemical analysis of 182 tumors. J Urol 171:604–611

    Article  CAS  Google Scholar 

  • Laurent G, Nonclercq D, Journé F, Brohée R, Toubeau G, Falmagne P, Heuson-Stiennon JA (1999) Characterization of a cell line established from diethylstilbestrol-induced renal tumors in Syrian hamsters. In Vitro Cell Dev Biol—Anim 35:339–344

    Article  PubMed  CAS  Google Scholar 

  • Li JJ, Li SA (1984) Estrogen-induced tumorigenesis in hamsters: roles for hormonal and carcinogenic activities. Arch Toxicol 55:108–110

    Article  Google Scholar 

  • Li JJ, Li SA (1990) Estrogen carcinogenesis in hamster tissues: a critical review. Endocr Rev 11:524–531

    Article  PubMed  CAS  Google Scholar 

  • Li JJ, Hou X, Banerjee SK, Liao DJ, Maggouta F, Norris JS, Li SA (1999) Overexpression and amplification of c-myc in the Syrian hamster kidney during estrogen carcinogenesis: a probable critical role in neoplastic transformation. Cancer Res 59:2340–2346

    PubMed  CAS  Google Scholar 

  • Li JJ, Weroha SJ, Davis MF, Tawfik O, Hou X, Li SA (2001) ER and PR in renomedullary interstitial cells during Syrian hamster estrogen-induced tumorigenesis: evidence for receptor-mediated oncogenesis. Endocrinology 142:4006–4014

    Article  PubMed  CAS  Google Scholar 

  • Liehr JG (1997) Hormone-associated cancer: mechanistic similarities between human breast cancer and estrogen-induced kidney carcinogenesis in hamsters. Environ Health Perspect 105:565–569

    Article  PubMed  CAS  Google Scholar 

  • Liehr JG (2001) Genotoxicity of the steroidal oestrogens oestrone and oestradiol: possible mechanism of uterine and mammary cancer development. Hum Reprod Update 7:273–281

    Article  PubMed  CAS  Google Scholar 

  • Liehr JG, Fang WF, Sirbasku DA, Ari-Ulubelen A (1986) Carcinogenicity of catechol estrogens in Syrian hamsters. J Steroid Biochem 24:353–356

    Article  PubMed  CAS  Google Scholar 

  • Lindblad P, Mellemgaard A, Schlehofer B, Adami HO, McCredie M, McLaughlin JK, Mandel JS (1995) International renal-cell cancer study. V. Reproductive factors, gynecologic operations and exogenous hormones. Int J Cancer 61:192–198

    Article  PubMed  CAS  Google Scholar 

  • Liu FT, Patterson RJ, Wang JL (2002) Intracellular functions of galectins. Biochim Biophys Acta 1572:263–273

    PubMed  CAS  Google Scholar 

  • López-Lucendo MF, Solís D, André S, Hirabayashi J, Kasai KI, Kaltner H, Gabius HJ, Romero A (2004) Growth-regulatory human galectin-1: crystallographic characterisation of the structural changes induced by single-site mutations and their impact on the thermodynamics of ligand binding. J Mol Biol 343:957–970

    Article  PubMed  CAS  Google Scholar 

  • Manning JC, Seyrek K, Kaltner H, André S, Sinowatz F, Gabius HJ (2004) Glycomic profiling of developmental changes in bovine testis by lectin histochemistry and further analysis of the most prominent alteration on the level of the glycoproteome by lectin blotting and lectin affinity chromatography. Histol Histopathol 19:1043–1060

    PubMed  CAS  Google Scholar 

  • Morris S, Ahmad N, André S, Kaltner H, Gabius HJ, Brenowitz M, Brewer F (2004) Quaternary solution structures of galectins-1, -3, and -7. Glycobiology 14:293–300

    Article  PubMed  CAS  Google Scholar 

  • Nagy N, Bronckart Y, Camby I, Legendre H, Lahm H, Kaltner H, Hadari Y, Van Ham P, Yeaton P, Pector JC, Zick Y, Salmon I, Danguy A, Kiss R, Gabius HJ (2002) Galectin-8 expression decreases in cancer as compared to normal and dysplastic human colon tissue and acts significantly on human colon cancer cell migration. Gut 50:392–401

    Article  PubMed  CAS  Google Scholar 

  • Nagy N, Legendre H, Engels O, André S, Kaltner H, Wasano K, Zick Y, Pector JC, Decaestecker C, Gabius HJ, Salmon I, Kiss R (2003) Refined prognostic evaluation in colon carcinoma using immunohistochemical galectin fingerprinting. Cancer 97:1849–1858

    Article  PubMed  Google Scholar 

  • Nogueira E, Gardesa A, Mohr U (1993) Experimental models of kidney tumors. J Cancer Res Clin Oncol 119:190–198

    Article  PubMed  CAS  Google Scholar 

  • Nonclercq D, Toubeau G, Wattiez R, LaurentG, Bernard A, Journe F, Falmagne P, Heuson-Stiennon JA (1998) Sublethal alterations and sustained cell proliferation associated with diethylstilbestrol-induced renal carcinogenesis in male Syrian golden hamsters. Eur J Morphol 36:83–96

    Article  PubMed  CAS  Google Scholar 

  • Nonclercq D, Lienard V, Zanen J, Laurent G, Toubeau G (2002) Phenotypic variation and dynamic topography of transformed cells in an experimental model of diethylstilbestrol-induced renal tumor in male Syrian hamster. Histochem J 34:487–497

    Article  PubMed  Google Scholar 

  • Orovan WL, Ryan ED (1989) Estrogen and progesterone binding sites in renal cell carcinoma. Urology 34:65–67

    Article  PubMed  CAS  Google Scholar 

  • Paron I, Scaloni A, Pines A, Bachi A, Liu FT, Puppin C, Pandolfi M, Ledda L, Di Loreto C, Damante G, Tell G (2003) Nuclear localization of galectin-3 in transformed thyroid cells: a role in transcriptional regulation. Biochem Biophys Res Commun 302:545–553

    Article  PubMed  CAS  Google Scholar 

  • Purkrábková T, Smetana K Jr, Dvoránková B, Holíková Z, Böck C, Lensch M, André S, Pytlík R, Liu FT, Klíma J, Smetana K, Motlík J, Gabius HJ (2003) New aspects of galectin functionality in nuclei of cultured bone marrow stromal and epidermal cells: biotinylated galectins as tool to detect specific binding sites. Biol Cell 95:535–545

    Article  PubMed  CAS  Google Scholar 

  • Rappl G, Abken H, Muche JM, Sterry W, Tilgen W, André S, Kaltner H, Ugurel S, Gabius HJ, Reinhold U (2002) CD4+CD7− leukemic T cells from patients with Sézary syndrome are protected from galectin-1-triggered T cell death. Leukemia 16:840–845

    Article  PubMed  CAS  Google Scholar 

  • Rotblat B, Niv H, André S, Kaltner H, Gabius HJ, Kloog Y (2004) Galectin-1(L11A) predicted from a computed galectin-1 farnesyl-binding pocket selectively inhibits Ras-GTP. Cancer Res 64:3112–3118

    Article  PubMed  CAS  Google Scholar 

  • Sanford GL, Owens MA, Odusanya BM (1993) Differential influence of dexamethasone on the activity and synthesis of β-galactoside specific lectin (galaptin) during postnatal lung development. Exp Lung Res 19:91–104

    Article  PubMed  CAS  Google Scholar 

  • Saussez S, Nonclercq D, Laurent G, Wattiez R, André S, Kaltner H, Gabius HJ, Kiss R, Toubeau G (2005) Toward functional glycomics by localization of tissue lectins: immunohistochemical galectin fingerprinting during diethylstilbestrol-induced kidney tumorigenesis in male Syrian hamster. Histochem Cell Biol 123:29–41

    Article  PubMed  CAS  Google Scholar 

  • Shimura T, Takenaka Y, Tsutsumi S, Hogan V, Kikuchi A, Raz A (2004) Galectin-3, a novel binding partner of β-catenin. Cancer Res 64:6363–6367

    Article  PubMed  CAS  Google Scholar 

  • Siebert HC, André S, Lu SY, Frank M, Kaltner H, van Kuik JA, Korchagina EY, Bovin NV, Tajkhorshid E, Kaptein R, Vliegenthart JFG, von der Lieth CW, Jiménez-Barbero J, Kopitz J, Gabius HJ (2003) Unique conformer selection of human growth-regulatory lectin galectin-1 for ganglioside GM1 versus bacterial toxins. Biochemistry 42:14762–14773

    Article  PubMed  CAS  Google Scholar 

  • Spicer SS, Schulte BA (1992) Diversity of cell glycoconjugates shown histochemically: a perspective. J Histochem Cytochem 40:1–38

    PubMed  CAS  Google Scholar 

  • Toubeau G, Nonclercq D, Laurent G, Brohee R, Zanen J, Van Cauwenberge A, Alexandre H, Falmagne P, Heuson-Stiennon JA (2001) Immunohistochemical analysis of diethylstilbestrol-induced renal tumors in adult male Syrian hamsters: evidence for relationship to peripheral nerve sheath tumors. Histochem Cell Biol 115:429–438

    PubMed  CAS  Google Scholar 

  • Unverzagt C, André S, Seifert J, Kojima S, Fink C, Srikrishna G, Freeze H, Kayser K, Gabius HJ (2002) Structure–activity profiles of complex biantennary glycans with core fucosylation and with/without additional α2,3/α2,6 sialylation: synthesis of neoglycoproteins and their properties in lectin assays, cell binding, and organ uptake. J Med Chem 45:478–491

    Article  PubMed  CAS  Google Scholar 

  • Villalobo AV, Nogales-Gonzalez A, Gabius HJ (2006) A guide to signalling pathways connecting protein–glycan interaction with the emerging versatile effector functionality of mammalian lectins. Trends Glycosci Glycotechnol (in press)

  • Wada T, Nishiyama K, Maeda M, Hara S, Tanaka N, Yasutomi M, Kurita T (1995) Combined chemoendocrine treatment with tegafur and tamoxifen for advanced renal cell carcinoma. Anticancer Res 15:1581–1584

    PubMed  CAS  Google Scholar 

  • Wattiez R, Nonclercq D, Journe F, Toubeau G, Zanen J, Falmagne P, Heuson-Stiennon JA (1996) Involvement of transforming growth factor α and its receptor in a model of DES-induced renal carcinogenesis in the Syrian hamster. Carcinogenesis 17:1615–1622

    Article  PubMed  CAS  Google Scholar 

  • Winyard PJ, Bao Q, Hughes RC, Woolf AS (1997) Epithelial galectin-3 during human nephrogenesis and childhood cystic diseases. J Am Soc Nephrol 8:1647–1657

    PubMed  CAS  Google Scholar 

  • Wu AM, Wu JH, Liu JH, Singh T, André S, Kaltner H, Gabius HJ (2004) Effects of polyvalency of glycotopes and natural modifications of human blood group ABH/Lewis sugars at the Galβ1-terminated core saccharides on the binding of domain-I of recombinant tandem-repeat-type galectin-4 from rat gastrointestinal tract (G4-N). Biochimie 86:317–326

    Article  PubMed  CAS  Google Scholar 

  • Young AN, Amin MB, Moreno CS, Lim SD, Cohen C, Petros JA, Marshall FF, Neish AS (2001) Expression profiling of renal epithelial neoplasms: a method for tumor classification and discovery of diagnostic molecular markers. Am J Pathol 158:1639–1651

    PubMed  CAS  Google Scholar 

Download references

Acknowledgements

R. Kiss and G. Laurent are Research Director and Senior Research Associate, respectively, of the National Fund for Scientific Research (Belgium). G. Laurent is the recipient of a grant (no. 3.4512.03) from the Belgian Fund for Medical Scientific Research and H.-J. Gabius of grants from the Mizutani Foundation for Glycoscience (Tokyo, Japan) and the Verein zur Förderung des biologisch-technologischen Fortschritts in der Medizin e.V. (Heidelberg, Germany). The expert technical assistance of G. Ninfa is gratefully acknowledged.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Sven Saussez.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Saussez, S., Lorfevre, F., Nonclercq, D. et al. Towards functional glycomics by localization of binding sites for tissue lectins: lectin histochemical reactivity for galectins during diethylstilbestrol-induced kidney tumorigenesis in male Syrian hamster. Histochem Cell Biol 126, 57–69 (2006). https://doi.org/10.1007/s00418-006-0146-9

Download citation

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00418-006-0146-9

Keywords

Navigation