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

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Breast Cancer Research and Treatment Aims and scope Submit manuscript

An Erratum to this article was published on 01 August 2005

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.

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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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Authors and Affiliations

  1. Shemyakin and Ovchinnikov Institute of Bioorganic Chemistry RAS, Moscow, Russia

    E. V. Moiseeva, E. M. Rapoport, N. V. Bovin, A. I. Miroshnikov, A. V. Chaadaeva & M. S. Krasilshschikova

  2. Department of Pathobiology, Utrecht University, Yalelaan 1, 80185, Utrecht, The Netherlands

    E. V. Moiseeva, E. M. Rapoport, J. E. van Dijk & W. Den Otter

  3. Russian Scientific Centre of Roentgen – Radiology, Moscow, Russia

    V. K. Bojenko

  4. Department of Cell Biology, Utrecht, The Netherlands

    Caspaar Bijleveld

Authors
  1. E. V. Moiseeva
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  2. E. M. Rapoport
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  3. N. V. Bovin
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  4. A. I. Miroshnikov
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  5. A. V. Chaadaeva
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  6. M. S. Krasilshschikova
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  7. V. K. Bojenko
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  8. Caspaar Bijleveld
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  9. J. E. van Dijk
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  10. W. Den Otter
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Correspondence to E. V. Moiseeva.

Additional information

An erratum to this artcile can be found at http://dx.doi.org/10.1007/s10549-005-1747-z

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Moiseeva, E.V., Rapoport, E.M., Bovin, N.V. et al. Galectins as markers of aggressiveness of mouse mammary carcinoma: towards a lectin target therapy of human breast cancer. Breast Cancer Res Treat 91, 227–241 (2005). https://doi.org/10.1007/s10549-005-0289-8

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