Breast Cancer Research and Treatment

, Volume 91, Issue 3, pp 227–241 | Cite as

Galectins as markers of aggressiveness of mouse mammary carcinoma: towards a lectin target therapy of human breast cancer

  • E. V.  Moiseeva
  • E. M.  Rapoport
  • N. V.  Bovin
  • A. I.  Miroshnikov
  • A. V.  Chaadaeva
  • M. S.  Krasilshschikova
  • V. K.  Bojenko
  • Caspaar  Bijleveld
  • J. E.  van Dijk
  • W.  Den Otter
Article

Summary

Galectins, β-galactoside binding proteins, expressed selectively in human breast carcinoma are attractive targets to employ lectin-aimed therapeutics. We examined β-galactoside binding potency of neoplastic cells using fluorescein-labelled synthetic glycoconjugates as probes for flow cytometry. As a result, surface β-galactoside binding proteins/galectins were discovered on mouse mammary carcinoma cells in vitro and in vivo unlike non-malignant cells from the several tissues; and asialo-GM1 ganglioside carbohydrate part - containing probe was the most specific one. However, in liver and lung metastatic cells galectins seem to be expressed within cytoplasm and/or nuclei. Galectin expression correlated directly with aggressive tumour potential in the A/Sn transplantable model similar to findings in several human breast carcinoma cell lines. However, galectin expression was reduced during tumour progression in more aggressive forms of spontaneous BLRB mammary carcinomas like it was shown for human breast carcinoma specimens. Analysis of the histopathological data led, however, to the conclusion that galectin expression hardly might be a suitable marker of aggressiveness of heterogeneous mammary carcinomas as the observed level of galectin expression is influenced by the amount of the stroma in a tumour sample and/or probably, galectin expression inversely correlates with tumour aggressiveness during the initial and advanced steps of mammary tumour progression. We conclude that surface β-galactoside binding proteins/galectins that are selectively expressed during mouse mammary carcinoma progression, similarly to human breast carcinomas, seem to be proper targets for asialo-GM1-vectored cytotoxics and our mouse model system might be a relevant instrument to further test novel modes of anti-breast cancer therapy.

Keywords

breast cancer galectins glycoconjugates metastases mouse model selectins 

Abbreviations

aGM1, Galβ1-3GalNAcβ1-4Galβ1-4Glcβ

asialo-GM1 ganglioside carbohydrate part

βGBP

β-galactoside binding protein

BC

breast cancer

BSA

bovine serum albumin

Glyc-PAA-fluo

polyacrylamide glycoconjugate probes labeled with fluorescein

LacNAc

Galβ1-4GlcNAcβ, lactosamine disaccharide

PAS

Periodic Acid -Schiff staining

PBS

phosphate buffered saline

PBA

PBS containing 0.2% BSA

PI

proliferation index

SiaLex

Neu5Acα2-3 Galβ1-4(Fucα1-3)GlcNAc tetrasaccharide

Tαα

Galβ1-3GalNAcα disaccharide

Versene solution

PBS containing 0.02% EDTA

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Copyright information

© Springer 2005

Authors and Affiliations

  • E. V.  Moiseeva
    • 1
    • 2
  • E. M.  Rapoport
    • 1
    • 2
  • N. V.  Bovin
    • 1
  • A. I.  Miroshnikov
    • 1
  • A. V.  Chaadaeva
    • 1
  • M. S.  Krasilshschikova
    • 1
  • V. K.  Bojenko
    • 3
  • Caspaar  Bijleveld
    • 4
  • J. E.  van Dijk
    • 2
  • W.  Den Otter
    • 2
  1. 1.Shemyakin and Ovchinnikov Institute of Bioorganic Chemistry RASMoscowRussia
  2. 2.Department of PathobiologyUtrecht UniversityUtrechtThe Netherlands
  3. 3.Russian Scientific Centre of Roentgen – RadiologyMoscowRussia
  4. 4.Department of Cell BiologyUtrechtThe Netherlands

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