Blocking Galactin-3 Binding Prevents Metastasis in Various Cancers

A small molecule derived from a glycoprotein that protects cod from freezing binds and inhibits galectin-3 and prevents metastasis in various cancers, including prostate adenocarcinoma.

Galectin-3 (gal3) is one of the 14 recognized mammalian lectins. This protein weighs approximately 30 kDa and, like all galectins, contains a carbohydrate-recognition-binding domain of about 130 amino acids that enables the specific binding of beta-galactosides. Gal3 is expressed in cells in the nucleus, cytoplasm, mitochondrion, cell surface, and extracellular space. This protein has been shown to be involved in cell adhesion, cell activation and chemoattraction, cell growth and differentiation, cell cycle, and apoptosis. Gal3 recognizes the Thomsen-Friedenreich disaccharide (TFD, galactose-N-acetylgalactosamine) that is present on the surface of most cancer cells and is involved in promoting angiogenesis, tumor-endothelial cell adhesion, and metastasis of prostate cancer cells, as well as evading immune surveillance through killing of activated T-cells.

Investigators at the University of Maryland School of Medicine (Baltimore, USA) isolated a glycopeptide (TDF100) from cod that presents the disaccharide (galactose-N-acetylgalactosamine) recognized by gal3.

They reported in the March 11, 2013, online edition of the journal Proceedings of the National Academy of Sciences of the United States of America (PNAS) that TFD100 blocked gal3-mediated angiogenesis, tumor-endothelial cell interactions, and metastasis of prostate cancer cells in mice at nanomolar levels. Apoptosis of activated T-cells—induced by either recombinant gal3 or prostate cancer patient serum-associated gal3—was inhibited by nanomolar concentrations of TFD100.

“This study is among the first to explore the therapeutic utility of a bioactive cod TFD-containing glycopeptide to inhibit prostate cancer from progressing,” said senior author Dr. Hafiz Ahmed, assistant professor of biochemistry and molecular biology at the University of Maryland School of Medicine. “The TFD (Thomsen-Friedenreich disaccharide) antigen in the fish protein is hidden in normal human cells but is exposed on the surface of cancer cells and is believed to play a key role in how cancer spreads.”

“The use of natural dietary products with antitumor activity is an important and emerging field of research,” said Dr. Ahmed. “Understanding how these products work could allow us to develop foods that also act as cancer therapeutics and agents for immunotherapy.”

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University of Maryland School of Medicine