Galectins as markers of aggressiveness of mouse mammary carcinoma: towards a lectin target therapy of human breast cancer.
Galectins, beta-galactoside binding proteins, expressed selectively in human breast carcinoma are attractive targets to employ lectin-aimed therapeutics. We examined beta-galactoside binding potency of neoplastic cells using fluorescein-labelled synthetic glycoconjugates as probes for flow cytometry. As a result, surface beta-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 beta-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.
Moiseeva
E V
EV
Shemyakin and Ovchinnikov Institute of Bioorganic Chemistry RAS, Moscow, Russia. evmoiseeva@yahoo.com
Rapoport
E M
EM
Bovin
N V
NV
Miroshnikov
A I
AI
Chaadaeva
A V
AV
Krasilshschikova
M S
MS
Bojenko
V K
VK
Bijleveld
Caspaar
C
van Dijk
J E
JE
Den Otter
W
W
D000818:Animals; D014408:Biomarkers, Tumor / Q000378:metabolism*; D002462:Cell Membrane / Q000378:metabolism; D002467:Cell Nucleus / Q000378:metabolism; D003593:Cytoplasm / Q000378:metabolism; D018450:Disease Progression; D005260:Female; D005677:G(M1) Ganglioside / Q000378:metabolism*; D005697:Galactosides / Q000378:metabolism*; D037161:Galectins / Q000378:metabolism*; D006001:Glycoconjugates; D066298:In Vitro Techniques; D008113:Liver Neoplasms / Q000378:metabolism / Q000556:secondary; D008297:Male; D008325:Mammary Neoplasms, Experimental / Q000378:metabolism* / Q000473:pathology / Q000628:therapy*; D051379:Mice; D008815:Mice, Inbred Strains; D017154:Stromal Cells / Q000378:metabolism / Q000473:pathology; D014407:Tumor Cells, Cultured / Q000637:transplantation
D014408:Biomarkers, Tumor; D005697:Galactosides; D037161:Galectins; D006001:Glycoconjugates; C007816:beta-galactoside; D005677:G(M1) Ganglioside; C018835:asialo GM1 ganglioside