Inhibition of prostate cancer bone metastasis by synthetic TF antigen mimic/galectin-3 inhibitor lactulose-L-leucine

Olga V. Glinskii, Sudha Sud, Valeri V. Mossine, Thomas P. Mawhinney, Douglas C. Anthony, Gennadi V. Glinsky, Kenneth Pienta, Vladislav V. Glinsky

Research output: Contribution to journalArticle

Abstract

Currently incurable, prostate cancer metastasis has a remarkable ability to spread to the skeleton. Previous studies demonstrated that interactions mediated by the cancer-associated Thomsen-Friedenreich glycoantigen (TF-Ag) and the carbohydrate-binding protein galectin-3 play an important role in several rate-limiting steps of cancer metastasis such as metastatic cell adhesion to bone marrow endothelium, homotypic tumor cell aggregation, and clonogenic survival and growth. This study investigated the ability of a synthetic small-molecular-weight nontoxic carbohydrate-based TF-Ag mimic lactulose-L-leucine (Lac-L-Leu) to inhibit these processes in vitro and, ultimately, prostate cancer bone metastasis in vivo. Using an in vivo mouse model, based on intracardiac injection of human PC-3 prostate carcinoma cells stably expressing luciferase, we investigated the ability of Lac-L-Leu to impede the establishment and growth of bone metastasis. Parallel-flow chamber assay, homotypic aggregation assay, modified Boyden chamber assay, and clonogenic growth assay were used to assess the effects of Lac-LLeu on tumor cell adhesion to the endothelium, homotypic tumor cell aggregation, transendothelial migration, and clonogenic survival and growth, respectively. We report that daily intraperitoneal administration of Lac-L-Leu resulted in a three-fold (P

Original languageEnglish (US)
Pages (from-to)65-73
Number of pages9
JournalNeoplasia
Volume14
Issue number1
DOIs
StatePublished - Jan 2012
Externally publishedYes

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Galectin 3
Lactulose
Bone Neoplasms
Synthetic Vaccines
Leucine
Prostatic Neoplasms
Neoplasm Metastasis
Cell Aggregation
Neoplasms
Cell Adhesion
Endothelium
Growth
Transendothelial and Transepithelial Migration
Survival
Bone Development
Luciferases
Skeleton
Prostate
Molecular Weight
Bone Marrow

ASJC Scopus subject areas

  • Cancer Research

Cite this

Glinskii, O. V., Sud, S., Mossine, V. V., Mawhinney, T. P., Anthony, D. C., Glinsky, G. V., ... Glinsky, V. V. (2012). Inhibition of prostate cancer bone metastasis by synthetic TF antigen mimic/galectin-3 inhibitor lactulose-L-leucine. Neoplasia, 14(1), 65-73. https://doi.org/10.1593/neo.111544

Inhibition of prostate cancer bone metastasis by synthetic TF antigen mimic/galectin-3 inhibitor lactulose-L-leucine. / Glinskii, Olga V.; Sud, Sudha; Mossine, Valeri V.; Mawhinney, Thomas P.; Anthony, Douglas C.; Glinsky, Gennadi V.; Pienta, Kenneth; Glinsky, Vladislav V.

In: Neoplasia, Vol. 14, No. 1, 01.2012, p. 65-73.

Research output: Contribution to journalArticle

Glinskii, OV, Sud, S, Mossine, VV, Mawhinney, TP, Anthony, DC, Glinsky, GV, Pienta, K & Glinsky, VV 2012, 'Inhibition of prostate cancer bone metastasis by synthetic TF antigen mimic/galectin-3 inhibitor lactulose-L-leucine', Neoplasia, vol. 14, no. 1, pp. 65-73. https://doi.org/10.1593/neo.111544
Glinskii, Olga V. ; Sud, Sudha ; Mossine, Valeri V. ; Mawhinney, Thomas P. ; Anthony, Douglas C. ; Glinsky, Gennadi V. ; Pienta, Kenneth ; Glinsky, Vladislav V. / Inhibition of prostate cancer bone metastasis by synthetic TF antigen mimic/galectin-3 inhibitor lactulose-L-leucine. In: Neoplasia. 2012 ; Vol. 14, No. 1. pp. 65-73.
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