Galectin-3 as a potential therapeutic target in tumors arising from malignant endothelia

Kim D. Johnson, Olga V. Glinskii, Valeri V. Mossine, James R. Turk, Thomas P. Mawhinney, Douglas C. Anthony, Carolyn J. Henry, Virginia H. Huxley, Gennadi V. Glinsky, Kenneth Pienta, Avraham Raz, Vladislav V. Glinsky

Research output: Contribution to journalArticle

Abstract

Angiosarcoma (ASA) in humans and hemangiosarcoma (HSA) in dogs are deadly neoplastic diseases characterized by an aggressive growth of malignant cells with endothelial phenotype, widespread metastasis, and poor response to chemotherapy. Galectin-3 (Gal-3), a β-galactoside-binding lectin implicated in tumor progression and metastasis, endothelial cell biology and angiogenesis, and regulation of apoptosis and neoplastic cell response to cytotoxic drugs, has not been studied before in tumors arising from malignant endothelia. Here, we tested the hypothesis that Gal-3 could be widely expressed in human ASA and canine HSA and could play an important role in malignant endothelial cell biology. Immunohistochemical analysis demonstrated that 100% of the human ASA (10 of 10) and canine HSA (17 of 17) samples analyzed expressed Gal-3. Two carbohydrate-based Gal-3 inhibitors, modified citrus pectin (MCP) and lactulosyl-L-leucine (LL), caused a dose-dependent reduction of SVR murine ASA cell clonogenic survival through the inhibition of Gal-3 anti-apoptotic function. Furthermore, both MCP and LL sensitized SVR cells to the cytotoxic drug doxorubicin to a degree sufficient to reduce the in vitro IC50 of doxorubicin by 10.7-fold and 3.6-fold, respectively. These results highlight the important role of Gal-3 in the biology of ASA and identify Gal-3 as a potential therapeutic target in tumors arising from malignant endothelial cells.

Original languageEnglish (US)
Pages (from-to)662-670
Number of pages9
JournalNeoplasia
Volume9
Issue number8
DOIs
StatePublished - Aug 2007
Externally publishedYes

Fingerprint

Galectin 3
Hemangiosarcoma
Endothelium
Neoplasms
Endothelial Cells
Therapeutics
Leucine
Doxorubicin
Cell Biology
Canidae
Neoplasm Metastasis
Galactosides
Lectins
Pharmaceutical Preparations
Inhibitory Concentration 50
Cell Survival
Carbohydrates
Dogs
Apoptosis
Phenotype

Keywords

  • Angiosarcoma
  • Apoptosis
  • Chemotherapy
  • Doxorubicin
  • Galectin-3

ASJC Scopus subject areas

  • Cancer Research

Cite this

Johnson, K. D., Glinskii, O. V., Mossine, V. V., Turk, J. R., Mawhinney, T. P., Anthony, D. C., ... Glinsky, V. V. (2007). Galectin-3 as a potential therapeutic target in tumors arising from malignant endothelia. Neoplasia, 9(8), 662-670. https://doi.org/10.1593/neo.07433

Galectin-3 as a potential therapeutic target in tumors arising from malignant endothelia. / Johnson, Kim D.; Glinskii, Olga V.; Mossine, Valeri V.; Turk, James R.; Mawhinney, Thomas P.; Anthony, Douglas C.; Henry, Carolyn J.; Huxley, Virginia H.; Glinsky, Gennadi V.; Pienta, Kenneth; Raz, Avraham; Glinsky, Vladislav V.

In: Neoplasia, Vol. 9, No. 8, 08.2007, p. 662-670.

Research output: Contribution to journalArticle

Johnson, KD, Glinskii, OV, Mossine, VV, Turk, JR, Mawhinney, TP, Anthony, DC, Henry, CJ, Huxley, VH, Glinsky, GV, Pienta, K, Raz, A & Glinsky, VV 2007, 'Galectin-3 as a potential therapeutic target in tumors arising from malignant endothelia', Neoplasia, vol. 9, no. 8, pp. 662-670. https://doi.org/10.1593/neo.07433
Johnson KD, Glinskii OV, Mossine VV, Turk JR, Mawhinney TP, Anthony DC et al. Galectin-3 as a potential therapeutic target in tumors arising from malignant endothelia. Neoplasia. 2007 Aug;9(8):662-670. https://doi.org/10.1593/neo.07433
Johnson, Kim D. ; Glinskii, Olga V. ; Mossine, Valeri V. ; Turk, James R. ; Mawhinney, Thomas P. ; Anthony, Douglas C. ; Henry, Carolyn J. ; Huxley, Virginia H. ; Glinsky, Gennadi V. ; Pienta, Kenneth ; Raz, Avraham ; Glinsky, Vladislav V. / Galectin-3 as a potential therapeutic target in tumors arising from malignant endothelia. In: Neoplasia. 2007 ; Vol. 9, No. 8. pp. 662-670.
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