Skip to main content
Log in

Breast Cancer Metastasis Alters Acetylcholinesterase Activity and the Composition of Enzyme Forms in Axillary Lymph Nodes

  • Published:
Breast Cancer Research and Treatment Aims and scope Submit manuscript

Abstract

Because of the probable involvement of cholinesterases (ChEs) in tumorigenesis, this research was addressed to ascertaining whether breast cancer metastasis alters the content of acetylcholinesterase (AChE) and/or butyrylcholinesterase (BuChE) in axillary lymph nodes (LN). ChE activity was assayed in nine normal (NLN) and seven metastasis-bearing nodes (MLN) from women. AChE and BuChE forms were characterised by sedimentation analyses, hydrophobic chromatography and western blotting. The origin of ChEs in LN was studied by lectin interaction. AChE activity dropped from 21.6 mU/mg (nmol of the substrate hydrolysed per minute and per milligram protein) in NLN to 3.8 mU/mg in MLN (p < 0.001), while BuChE activity (3.6 mU/mg) was little affected. NLN contained globular amphiphilic AChE dimers (G2 A, 35%), monomers (G2 A, 30%), hydrophilic tetramers (G4 H, 8%), and asymmetric species (A4, 23%, and A8, 4%); MLN displayed only G2 A (65%) and G2 A (35%) AChE forms. NLN and MLN contained G4 H (79%), G4 A (7%), and G1 H (14%) BuChE components. Neither the binding of ChE forms with lectins and antibodies nor the subunit size were altered by metastasis. The higher level of AChE in NLN than in brain and the specific pattern of AChE forms in NLN support its role in immunity. The different profile of AChE forms in NLN and MLN may be useful for diagnosis.

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

References

  1. Massoulié J, Anselmet A, Bon S, Krejci E, Legay C, Morel N, Simon D: The polymorphism of acetylcholinesterase: post-translational processing, quaternary associations and localization. Chem Biol Interact 119-120: 29-42, 1999

    Google Scholar 

  2. Taylor P, Radic Z: The cholinesterases: from genes to proteins. Annu Rev Pharmacol Toxicol 34: 281-320, 1994

    Google Scholar 

  3. Li B, Stribley JA, Ticu A, Xie W, Schopfer LM, Hammond P, Brimijoin S, Hinrichs SH, Lockridge O: Abundant tissue butyrylcholinesterase and its possible function in the acetylcholinesterase knockout mouse. J Neurochem 75: 1320-1331, 2000

    Google Scholar 

  4. Jbilo O, L'Hermite Y, Talesa V, Toutant JP, Chatonnet A: Acetylcholinesterase and butyrylcholinesterase expression in adult rabbit tissues and during development. Eur J Biochem 225: 115-124, 1994

    Google Scholar 

  5. Boschetti N, Brodbeck U: The membrane anchor of mammalian brain acetylcholinesterase consists of a single glycosylated protein of 22 kDa. FEBS Lett 380: 133-136, 1996

    Google Scholar 

  6. Perrier AL, Massoulié J, Krejci E: PRiMA: the membrane anchor of acetylcholinesterase in the brain. Neuron 33: 275-285, 2002

    Google Scholar 

  7. Feng G, Krejci E, Molgo J, Cunningham A, Massoulié J, Sanes JR: Genetic analysis of collagen Q: roles in acetylcholinesterase and butyrylcholinesterase assembly and in synaptic structure and function. J Cell Biol 144: 1349-1360, 1999

    Google Scholar 

  8. Zakut H, Lapidot-Lifson Y, Beeri R, Ballin A, Soreq H: In vivo gene amplification in non-cancerous cells: cholinesterase genes and oncogenes amplify in thrombocytopenia associated with lupus erythematosus. Mutat Res 276: 275-284, 1992

    Google Scholar 

  9. Zakut H, Ehrlich G, Ayalon A, Prody CA, Malinger G, Seidman S, Ginzberg D, Kehlenbach R, Soreq H: Acetylcholinesterase and butyrylcholinesterase genes coamplify in primary ovarian carcinomas. J Clin Invest 86: 900-908, 1990

    Google Scholar 

  10. Grisaru D, Sternfeld M, Eldor A, Glick D, Soreq H: Structural roles of acetylcholinesterase variants in biology and pathology. Eur J Biochem 264: 672-686, 1999

    Google Scholar 

  11. García-Ayllón MS, Saez-Valero J, Muñoz-Delgado E, Vidal CJ: Identification of hybrid cholinesterase forms consisting of acetyl-and butyrylcholinesterase subunits in human glioma. Neuroscience 107: 199-208, 2001

    Google Scholar 

  12. Sáez-Valero J, Vidal CJ: Biochemical properties of acetyland butyrylcholinesterase in human meningioma. Biochim Biophys Acta 1317: 210-218, 1996

    Google Scholar 

  13. Sáez-Valero J, Poza-Cisneros G, Vidal CJ: Molecular forms of acetyl-and butyrylcholinesterase in human glioma. Neurosci Lett 206: 173-176, 1996

    Google Scholar 

  14. García-Ayllón MS, Sáez-Valero J, Piqueras-López C, Vidal CJ: Characterization of molecular forms of acetyl-and butyrylcholinesterase in human acoustic neurinomas. Neurosci Lett 274: 56-60, 1999

    Google Scholar 

  15. Ruiz-Espejo F, Cabezas-Herrera J, Illana J, Campoy FJ, Vidal CJ: Cholinesterase activity and acetylcholinesterase glycosylation are altered in human breast cancer. Breast Cancer Res Tr 72: 11-22, 2002

    Google Scholar 

  16. Moral-Naranjo MT, Cabezas-Herrera J, Vidal CJ: Molecular forms of acetyl-and butyrylcholinesterase in normal and dystrophic mouse brain. J Neurosci Res 43: 224-234, 1996

    Google Scholar 

  17. Moral-Naranjo MT, Campoy FJ, Cabezas-Herrera J, Vidal CJ: Increased butyrylcholinesterase levels in microsomal membranes of dystrophic Lama2 dy mouse muscle. J Neurochem 73: 1138-1144, 1999

    Google Scholar 

  18. Cabezas-Herrera J, Moral-Naranjo MT, Campoy FJ, Vidal CJ: Glycosylation of acetylcholinesterase forms in microsomal membranes from normal and dystrophic Lama2 dy mouse muscle. J Neurochem 69: 1964-1974, 1997

    Google Scholar 

  19. Laemmli UK: Cleavage of structural protein during the assembly of the head of bacteriophage T4. Nature 227: 680-685, 1970

    Google Scholar 

  20. Massoulié J: The origin of the molecular diversity and functional anchoring of cholinesterases. Neurosignals 11: 130-143, 2002

    Google Scholar 

  21. Altamirano CV, Lockridge O: Conserved aromatic residues of the C-terminus of human butyrylcholinesterase mediate the association of tetramers. Biochemistry 38: 13414-13422, 1999

    Google Scholar 

  22. Toutant JP, Richards MK, Krall JA, Rosenberry TL: Molecular forms of acetylcholinesterase in two sublines of human erythroleukemia K562 cells. Sensitivity or resistance to phosphatidylinositol specific phospholipase C and biosynthesis. Eur J Biochem 187: 31-38, 1990

    Google Scholar 

  23. Gómez JL, García-Ayllón MS, Campoy FJ, Vidal CJ: Muscular dystrophy alters the processing of light acetylcholinesterase but not butyrylcholinesterase forms in liver of Lama2dy mice. J Neurosci Res 62: 134-145, 2000

    Google Scholar 

  24. Kawashima K, Takeshi F: Extraneuronal cholinergic system in lymphocytes. Pharmacol Therapeut 86: 29-48, 2000

    Google Scholar 

  25. Velan B, Grosfeld H, Kronman C, Leitner M, Gozes Y, Lazar A, Flashner Y, Marcus D, Cohen S, Shafferman A: The effect of elimination of intersubunit disulfide bonds on the activity, assembly, and secretion of recombinant human acetylcholinesterase. Expression of acetylcholinesterase Cys-580→Ala mutant. J Biol Chem 266: 23977-23984, 1991

    Google Scholar 

  26. Blong RM, Bedows E, Lockridge O: Tetramerization domain of human butyrylcholinesterase is at the C-terminus. Biochem J 327: 747-757, 1997

    Google Scholar 

  27. Rakhawy MT, Tarkhan AA, Zakaria AM: Cholinesterase activity in some human lymphatic organs. Acta Anat 95: 130-141, 1976

    Google Scholar 

  28. Sáez-Valero J, Tornel PL, Muñoz-Delgado E, Vidal CJ: Amphiphilic and hydrophilic forms of acetyl-and butyrylcholinesterase in human brain. J Neurosci Res 35: 678-689, 1993

    Google Scholar 

  29. Richier P, Arpagaus M, Toutant JP: Glycolipid-anchored acetylcholinesterase from rabbit lymphocytes and erythrocytes differ in their sensitivity to phosphatidylinositol-specific phospholipase C. Biochim Biophys Acta 1112: 83-88, 1992

    Google Scholar 

  30. Bartha E, Rakonczay Z, Kasa P, Hollan S, Gyevai A: Molecular forms of human lymphocyte membrane-bound acetylcholinesterase. Life Sci 41: 1853-1860, 1987

    Google Scholar 

  31. Vidal CJ: Glycosylation of cholinesterases and its alteration in some pathological processes. Recent Res Devel Neurochem 1: 37-54, 1996

    Google Scholar 

  32. Fernández HL, Moreno RD, Inestrosa NC: Tetrameric (G4) acetylcholinesterase: structure, localization and physiological regulation. J Neurochem 66: 1335-1346, 1996

    Google Scholar 

  33. Lampert IA, Van Noorden S: Acetyl cholinesterase is expressed in the follicular dendritic cells of germinal centres: differences between normal and neoplastic follicles. J Pathol 180: 169-174, 1996

    Google Scholar 

  34. Lev-Lehman E, Ginzberg D, Hornreich G, Ehrlich G, Meshorer A, Eckstein F, Soreq H, Zakut H: Antisense inhibition of acetylcholinesterase gene expression causes transient hematopoietic alterations in vivo. Gene Ther 2: 1-9, 1994

    Google Scholar 

  35. Soreq H, Patinkin D, Lev-Lehman E, Grifman M, Ginzberg D, Eckstein F, Zakut H: Antisense oligonucleotide inhibition of acetylcholinesterase gene expression induces progenitor cell expansion and suppresses hematopoietic apoptosis ex vivo. P Natl Acad Sci USA 91: 7907-7911, 1994

    Google Scholar 

  36. Grisaru D, Deutsch SI, Shapira J, Pick M, Sternfeld M, Melamed-Book N, Kaufer D, Galyam N, Gait MJ, Owen D, Lessing JB, Eldor A, Soreq H: ARP, a peptide derived from the stress-associated acetylcholinesterase variant, has hematopoietic growth promoting activities. Mol Med 7: 93-105, 2001

    Google Scholar 

  37. Topilko A, Kaillou B: Acetylcholinesterase in human thymus cells. Blood 66: 891-895, 1985

    Google Scholar 

  38. Ando T, Fujii T, Kawashima K: Expression of three acetylcholinesterase mRNAs in human lymphocytes. Jpn J Pharmacol 79(Suppl. I): 289P, 1999

  39. Rinner I, Globerson A, Kawashima K, Korsatko W, Schauenstein K: A possible role for acetylcholine in the dialogue between thymocytes and thymic stroma. Neuroimmunomodulation 6: 51-55, 1999

    Google Scholar 

  40. Johnson VJ, Rosenberg AM, Lee K, Blakley BR: Increased Tlymphocyte dependent antibody production in female SJL/J mice following exposure to commercial grade malathion. Toxicology 170: 119-129, 2002

    Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Rights and permissions

Reprints and permissions

About this article

Cite this article

Ruiz-Espejo, F., Cabezas-Herrera, J., Illana, J. et al. Breast Cancer Metastasis Alters Acetylcholinesterase Activity and the Composition of Enzyme Forms in Axillary Lymph Nodes. Breast Cancer Res Treat 80, 105–114 (2003). https://doi.org/10.1023/A:1024461108704

Download citation

  • Issue Date:

  • DOI: https://doi.org/10.1023/A:1024461108704

Navigation