Histochemistry and Cell Biology

, Volume 130, Issue 3, pp 567–581

Cell-type-specific expression of murine multifunctional galectin-3 and its association with follicular atresia/luteolysis in contrast to pro-apoptotic galectins-1 and -7

  • Michaela Lohr
  • Herbert Kaltner
  • Martin Lensch
  • Sabine André
  • Fred Sinowatz
  • Hans-Joachim Gabius
Original Paper

Abstract

Galectin-3 is a multifunctional protein with modular design. A distinct expression profile was determined in various murine organs when set into relation to homodimeric galectins-1 and -7. Fittingly, the signature of putative transcription-factor-binding sites in the promoter region of the galectin-3 gene affords a toolbox for a complex combinatorial regulation, distinct from the respective sequence stretches in galectins-1 and -7. A striking example for cell-type specificity was the ovary, where these two lectins were confined to the surface epithelium. Immunohistochemically, galectin-3 was found in macrophages of the cortical interstitium between developing follicles and medullary interstitium, matching the distribution of the F4/80 antigen. With respect to atresia and luteolysis strong signals in granulosa cells of atretic preantral but not antral follicles and increasing positivity in corpora lutea upon regression coincided with DNA fragmentation. Labeled galectin-3 revealed lactose-inhibitable binding to granulosa cells. Also, slender processes of vital granulosa cells which extended into the zona pellucida were positive. This study demonstrates cell-type specificity and cycle-associated regulation for galectin-3 with increased presence in atretic preantral follicles and in late stages of luteolysis.

Keywords

Atresia Corpus luteum Granulosa cell Lectin Ovary 

Supplementary material

418_2008_465_MOESM1_ESM.doc (116 kb)
MOESM1 (DOC 116 kb)

References

  1. 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 279:10841–10847PubMedCrossRefGoogle Scholar
  2. André S, Liu B, Gabius HJ, Roy R (2003) First demonstration of differential inhibition of lectin binding by synthetic tri- and tetravalent glycoclusters from cross-coupling of rigidified 2-propynyl lactoside. Org Biomol Chem 1:3909–3916PubMedCrossRefGoogle Scholar
  3. André S, Kaltner H, Furuike T, Nishimura SI, Gabius HJ (2004) 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 15:87–98PubMedCrossRefGoogle Scholar
  4. André S, Kaltner H, Lensch M, Russwurm R, Siebert HC, Fallsehr C, Tajkhorshid E, Heck AJR, von Knebel-Döberitz M, Gabius HJ, Kopitz J (2005) 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 114:46–57PubMedCrossRefGoogle Scholar
  5. André S, Pei Z, Siebert HC, Ramström O, Gabius HJ (2006) Glycosyldisulfides from dynamic combinatorial libraries as O-glycoside mimetics for plant and endogenous lectins: their reactivities in solid-phase and cell assays and conformational analysis by molecular dynamics simulations. Bioorg Med Chem 14:6314–6326PubMedCrossRefGoogle Scholar
  6. André S, Sanchez-Ruderisch H, Nakagawa H, Buchholz M, Kopitz J, Forberich P, Kemmner W, Böck C, Deguchi K, Detjen KM, Wiedenmann B, von Knebel-Döberitz M, Gress TM, Nishimura SI, Rosewicz S, Gabius HJ (2007) Tumor suppressor p16INK4a: modulator of glycomic profile and galectin-1 expression to increase susceptibility to carbohydrate-dependent induction of anoikis in pancreatic carcinoma cells. FEBS J 273:3233–3256CrossRefGoogle Scholar
  7. Arnoys EJ, Wang JL (2007) Dual localization: proteins in extracellular and intracellular compartments. Acta Histochem 109:89–110PubMedCrossRefGoogle Scholar
  8. Aubin JE, Gupta AK, Bhargava U, Turksen K (1996) Expression and regulation of galectin-3 in rat osteoblastic cells. J Cell Physiol 169:468–480PubMedCrossRefGoogle Scholar
  9. Bernerd F, Sarasin A, Magnaldo T (1999) Galectin-7 overexpression is associated with the apoptotic process in UVB-induced sunburn keratinocytes. Proc Natl Acad Sci USA 96:11329–11334PubMedCrossRefGoogle Scholar
  10. Carambula SF, Matikainen T, Lynch MP, Flavell RA, Gonçalves PBD, Tilly JL, Rueda BR (2002) Caspase-3 is a pivotal mediator of apoptosis during regression of the ovarian corpus luteum. Endocrinology 143:1495–1501PubMedCrossRefGoogle Scholar
  11. Choe YS, Shim C, Choi D, Lee CS, 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 48:261–266PubMedCrossRefGoogle Scholar
  12. Choi EJ, Ha CM, Choi J, Kang SS, Choi WS, Park SK, Kim K, Lee BJ (2001) Low-density cDNA array-coupled to PCR differential display identifies new estrogen-responsive genes during the postnatal differentiation of the rat hypothalamus. Mol Brain Res 97:115–128PubMedCrossRefGoogle Scholar
  13. Colnot C, Sidhu SS, Balmain N, Poirier F (2001) Uncoupling of chondrocyte death and vascular invasion in mouse galectin-3 null mutant bones. Dev Biol 229:203–214PubMedCrossRefGoogle Scholar
  14. Davis JS, Rueda BR (2002) The corpus luteum: an ovarian structure with maternal instincts and suicidal tendencies. Front Biosci 7:d1949–d1978PubMedCrossRefGoogle Scholar
  15. Fischer C, Sanchez-Ruderisch H, Welzel M, Wiedenmann B, Sakai T, André S, Gabius HJ, Khachigian L, Detjen KM, Rosewicz S (2005) Galectin-1 interacts with the α5β1 fibronectin receptor to restrict carcinoma cell growth via induction of p21 and p27. J Biol Chem 280:37266–37277PubMedCrossRefGoogle Scholar
  16. Gabius HJ (1997) Animal lectins. Eur J Biochem 243:543–576PubMedCrossRefGoogle Scholar
  17. Gabius HJ (2006) Cell surface glycans: the why and how of their functionality as biochemical signals in lectin-mediated information transfer. Crit Rev Immunol 26:43–79PubMedGoogle Scholar
  18. Gabius HJ (ed) (2008) The sugar code. Fundamentals of glycosciences. Wiley/VCH, WeinheimGoogle Scholar
  19. 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 95:269–277PubMedCrossRefGoogle Scholar
  20. Gabius HJ, Siebert HC, André S, Jiménez-Barbero J, Rüdiger H (2004) Chemical biology of the sugar code. ChemBioChem 5:740–764Google Scholar
  21. Gong HC, Honjo Y, Nangia-Makker P, Hogan V, Mazurak N, Bresalier RS, Raz A (1999) The NH2 terminus of galectin-3 governs cellular compartmentalization and functions in cancer cells. Cancer Res 59:6239–6245PubMedGoogle Scholar
  22. Honjo Y, Inohara H, Akahani S, Yoshii T, Takenaka Y, Yoshida JI, Hattori K, Tomiyama Y, Raz A, Kubo T (2000) Expression of cytoplasmic galectin-3 as a prognostic marker in tongue carcinoma. Clin Cancer Res 6:4635–4640PubMedGoogle Scholar
  23. Hsu SY, Lai RJM, Finegold M, Hsueh AJW (1996) Targeted overexpression of Bcl-2 in ovaries of transgenic mice leads to decreased follicle apoptosis, enhanced folliculogenesis, and increased germ cell tumorigenesis. Endocrinology 137:4837–4843PubMedCrossRefGoogle Scholar
  24. Jeffery CJ (2003) Multifunctional proteins: examples of gene sharing. Ann Med 35:28–35PubMedCrossRefGoogle Scholar
  25. Kaltner H, Seyrek K, Heck A, Sinowatz F, Gabius HJ (2002) Galectin-1 and galectin-3 in fetal development of bovine respiratory and digestive tracts. Cell Tissue Res 307:35–46PubMedCrossRefGoogle Scholar
  26. Kayser K, Trott J, Böhm G, Huber M, Kaltner H, André S, Gabius HJ (2005) Localized fibrous tumors (LFTs) of the pleura: clinical data, asbestos burden, and syntactic structure analysis applied to newly defined angiogenic/growth-regulatory effectors. Pathol Res Pract 201:791–801PubMedCrossRefGoogle Scholar
  27. Kim H, Lee J, Hyun JW, Park JW, Joo HG, Shin T (2007) Expression and immunohistochemical localization of galectin-3 in various mouse tissues. Cell Biol Int 31:655–662PubMedCrossRefGoogle Scholar
  28. Kopitz J, von Reitzenstein C, André S, Kaltner H, Uhl J, Ehemann V, Cantz M, Gabius HJ (2001) Negative regulation of neuroblastoma cell growth by carbohydrate-dependent surface binding of galectin-1 and functional divergence from galectin-3. J Biol Chem 276:35917–35923PubMedCrossRefGoogle Scholar
  29. 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 22:6277–6288PubMedCrossRefGoogle Scholar
  30. Kübler D, Hung CW, Dam TK, Kopitz J, André S, Kaltner H, Lohr M, Manning JC, He L, Wang H, Middelberg A, Brewer CF, Reed J, Lehmann WD, Gabius HJ (2008) Phosphorylated human galectin-3: facile large-scale preparation of active lectin and detection of structural changes by CD spectroscopy. Biochim Biophys Acta 1780:716–722PubMedGoogle Scholar
  31. Lensch M, Lohr M, Russwurm R, Vidal M, Kaltner H, André S, Gabius HJ (2006) Unique sequence and expression profiles of rat galectins-5 and -9 as a result of species-specific gene divergence. Int J Biochem Cell Biol 38:1741–1758PubMedCrossRefGoogle Scholar
  32. Liu FT, Patterson RJ, Wang JL (2002) Intracellular functions of galectins. Biochim Biophys Acta 1572:263–273PubMedGoogle Scholar
  33. Lohr M, Lensch M, André S, Kaltner H, Siebert HC, Smetana K Jr, Sinowatz F, Gabius HJ (2007) Murine homodimeric adhesion/growth-regulatory galectins-1, -2 and -7: comparative profiling of gene/promoter sequences by database mining, of expression by RT-PCR/immunohistochemistry and of contact sites for carbohydrate ligands by computational chemistry. Folia Biol (Praha) 53:109–128Google Scholar
  34. Matsuda-Minehata F, Inoue N, Goto Y, Manabe N (2006) The regulation of ovarian granulosa cell death by pro- and anti-apoptotic molecules. J Reprod Dev 52:695–705PubMedCrossRefGoogle Scholar
  35. Moisa A, Fritz P, Eck A, Wehner HD, Mürdter T, Simon W, Gabius HJ (2007) Growth/adhesion-regulatory tissue lectin galectin-3: stromal presence but not cytoplasmic/nuclear expression in tumor cells as a negative prognostic factor in breast cancer. Anticancer Res 27:2131–2140PubMedGoogle Scholar
  36. Nakahara S, Raz A (2007) Regulation of cancer-related gene expression by galectin-3 and the molecular mechanism of its nuclear import pathway. Cancer Metastasis Rev 26:605–610PubMedCrossRefGoogle Scholar
  37. Nio J, Iwanaga T (2007) Galectins in the mouse ovary: concomitant expression of galectin-3 and progesterone degradation enzyme (20α-HSD) in the corpus luteum. J Histochem Cytochem 55:423–432PubMedCrossRefGoogle Scholar
  38. Ortega N, Behonick DJ, Colnot C, Cooper DNW, Werb Z (2005) Galectin-3 is a downstream regulator of matrix metalloproteinase-9 function during endochondral bone formation. Mol Biol Cell 16:3028–3039PubMedCrossRefGoogle Scholar
  39. Perez GI, Robles R, Knudson CM, Flaws JA, Korsmeyer SJ, Tilly JL (1999) Prolongation of ovarian lifespan into advanced chronological age by Bax-deficiency. Nat Genet 21:200–203PubMedCrossRefGoogle Scholar
  40. Piantelli M, Iacobelli S, Almadori G, Iezzi M, Tinari N, Natoli C, Cadoni G, Lauriola L, Ranelletti FO (2002) Lack of expression of galectin-3 is associated with a poor outcome in node-negative patients with laryngeal squamous-cell carcinoma. J Clin Oncol 20:3850–3856PubMedCrossRefGoogle Scholar
  41. Plzák J, Smetana K Jr, Hrdlicková E, Kodet R, Holíková Z, Liu FT, Dvořánková B, Kaltner H, Betka J, Gabius HJ (2001) Expression of galectin-3-reactive ligands in squamous cancer and normal epithelial cells as a marker of differentiation. Int J Oncol 19:59–64PubMedGoogle Scholar
  42. Plzák J, Betka J, Smetana K Jr, Chovanec M, Kaltner H, André S, Kodet R, Gabius HJ (2004) Galectin-3—an emerging prognostic indicator in advanced head and neck carcinoma. Eur J Cancer 40:2324–2330PubMedCrossRefGoogle Scholar
  43. Polyak K, Xia Y, Zweier JL, Kinzler KW, Vogelstein B (1997) A model for p53-induced apoptosis. Nature 389:300–305PubMedCrossRefGoogle Scholar
  44. Ramasamy S, Duraisamy S, Barbashov S, Kawano T, Kharbanda S, Kufe D (2007) The MUC1 and galectin-3 oncoproteins function in a microRNA-dependent regulatory loop. Mol Cell 27:992–1004PubMedCrossRefGoogle Scholar
  45. Rappl G, Abken H, Muche JM, Sterry W, Tilgen W, André S, Kaltner H, Ugurel S, Gabius HJ, Reinhold U (2002) CD4+CD7leukemic T cells from patients with Sézary syndrome are protected from galectin-1-triggered T cell death. Leukemia 16:840–845PubMedCrossRefGoogle Scholar
  46. Ratts VS, Flaws JA, Kolp R, Sorenson CM, Tilly JL (1995) Ablation of bcl-2 gene expression decreases the numbers of oocytes and primordial follicles established in the post-natal female mouse gonad. Endocrinology 136:3665–3668PubMedCrossRefGoogle Scholar
  47. Sato Y, Suzuki T, Hidaka K, Sato H, Ito K, Ito S, Sasano H (2003) Immunolocalization of nuclear transcription factors, DAX-1 and COUP-TF II, in the normal human ovary: correlation with adrenal 4 binding protein/steroidogenic factor-1 immunolocalization during the menstrual cycle. J Clin Endocrinol Metab 88:3415–3420PubMedCrossRefGoogle Scholar
  48. Saussez S, Cucu DR, Decaestecker C, Chevalier D, Kaltner H, André S, Wacreniez A, Toubeau G, Camby I, Gabius HJ, Kiss R (2006) Galectin-7 (p53-induced gene 1): a new prognostic predictor of recurrence and survival in stage IV hypopharyngeal cancer. Ann Surg Oncol 13:999–1009PubMedCrossRefGoogle Scholar
  49. Sheikholeslam-Zadeh R, Decaestecker C, Delbrouck C, Danguy A, Salmon I, Zick Y, Kaltner H, Hassid S, Gabius HJ, Kiss R, Choufani G (2001) The levels of expression of galectin-3, but not of galectin-1 and galectin-8, correlate with apoptosis in human cholesteatomas. Laryngoscope 111:1042–1047PubMedCrossRefGoogle Scholar
  50. Smetana K Jr, Dvořánková B, Chovanec M, Bouček J, Klíma J, Motlík J, Lensch M, Kaltner H, André S, Gabius HJ (2006) Nuclear presence of adhesion-/growth-regulatory galectins in normal/malignant cells of squamous epithelial origin. Histochem Cell Biol 125:171–182PubMedCrossRefGoogle Scholar
  51. Smith ME (2001) Phagocytic properties of microglia in vitro: implications for a role in multiple sclerosis and EAE. Microsc Res Tech 54:81–94PubMedCrossRefGoogle Scholar
  52. Solís D, Jiménez-Barbero J, Kaltner H, Romero A, Siebert HC, von der Lieth CW, Gabius HJ (2001) Towards defining the role of glycans as hardware in information storage and transfer: basic principles, experimental approaches and recent progress. Cells Tissues Organs 168:5–23PubMedCrossRefGoogle Scholar
  53. Stierstorfer B, Kaltner H, Neumüller C, Sinowatz F, Gabius HJ (2000) Temporal and spatial regulation of expression of two galectins during kidney development of the chicken. Histochem J 32:325–336PubMedCrossRefGoogle Scholar
  54. Stock M, Schäfer H, Stricker S, Gross G, Mundlos S, Otto F (2003) Expression of galectin-3 in skeletal tissues is controlled by Runx2. J Biol Chem 278:17360–17367PubMedCrossRefGoogle Scholar
  55. Sturm A, Lensch M, André S, Kaltner H, Wiedenmann B, Rosewicz S, Dignass AU, Gabius HJ (2004) Human galectin-2: novel inducer of T cell apoptosis with distinct profile of caspase activation. J Immunol 173:3825–3837PubMedGoogle Scholar
  56. Ullmann SL, Russell AJ, Mason JI, Selwood L (2003) Species differences in the ovarian distribution of 3β-hydroxysteroid dehydrogenase/Δ5 → 4 isomerase (3β-HSD) in two marsupials: the brushtail possum Trichosurus vulpecula and the grey, short-tailed opossum Monodelphis domestica. Reproduction 125:65–73PubMedCrossRefGoogle Scholar
  57. Villalobo A, Nogales-González A, Gabius HJ (2006) A guide to signaling pathways connecting protein–glycan interaction with the emerging versatile effector functionality of mammalian lectins. Trends Glycosci Glycotechnol 18:1–37Google Scholar
  58. Walzel H, Brock J, Pöhland R, Vanselow J, Tomek W, Schneider F, Tiemann U (2004) Effects of galectin-1 on regulation of progesterone production in granulosa cells from pig ovaries in vitro. Glycobiology 14:871–881PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag 2008

Authors and Affiliations

  • Michaela Lohr
    • 1
  • Herbert Kaltner
    • 1
  • Martin Lensch
    • 1
  • Sabine André
    • 1
  • Fred Sinowatz
    • 2
  • Hans-Joachim Gabius
    • 1
  1. 1.Institute of Physiological Chemistry, Faculty of Veterinary MedicineLudwig Maximilians UniversityMunichGermany
  2. 2.Institute of Veterinary Anatomy, Faculty of Veterinary MedicineLudwig Maximilians UniversityMunichGermany

Personalised recommendations