Cod glycopeptide with picomolar affinity to galectin-3 suppresses T-cell apoptosis and prostate cancer metastasis

Proc Natl Acad Sci U S A. 2013 Mar 26;110(13):5052-7. doi: 10.1073/pnas.1202653110. Epub 2013 Mar 11.


Cancer metastasis and immune suppression are critical issues in cancer therapy. Here, we show that a β-galactoside-binding lectin [galectin-3 (gal3)] that recognizes the Thomsen-Friedenreich disaccharide (TFD, Galβ1,3GalNAc) present on the surface of most cancer cells 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. To block gal3-mediated interactions, we purified a glycopeptide from cod (designated TFD100) that binds gal3 with picomolar affinity. TFD100 blocks gal3-mediated angiogenesis, tumor-endothelial cell interactions, and metastasis of prostate cancer cells in mice at nanomolar levels. Moreover, apoptosis of activated T cells induced by either recombinant gal3 or prostate cancer patient serum-associated gal3 was inhibited at nanomolar concentration of TFD100. Because the gal3-TFD interaction is a key factor driving metastasis in most epithelial cancers, this high-affinity TFD100 should be a promising antimetastatic agent for the treatment of various cancers, including prostate adenocarcinoma.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Adenocarcinoma / drug therapy*
  • Adenocarcinoma / metabolism
  • Adenocarcinoma / pathology
  • Animals
  • Antifreeze Proteins / chemistry
  • Antifreeze Proteins / isolation & purification
  • Antifreeze Proteins / pharmacology*
  • Antigens, Tumor-Associated, Carbohydrate / chemistry
  • Antigens, Tumor-Associated, Carbohydrate / metabolism
  • Antineoplastic Agents / chemistry
  • Antineoplastic Agents / isolation & purification
  • Antineoplastic Agents / pharmacology*
  • Apoptosis / drug effects*
  • Fish Proteins / chemistry
  • Fish Proteins / isolation & purification
  • Fish Proteins / pharmacology*
  • Gadus morhua*
  • Galectin 3 / metabolism*
  • Human Umbilical Vein Endothelial Cells
  • Humans
  • Jurkat Cells
  • Male
  • Mice
  • Neoplasm Metastasis
  • Neoplasm Proteins / metabolism*
  • Neovascularization, Pathologic / drug therapy
  • Neovascularization, Pathologic / metabolism
  • Neovascularization, Pathologic / pathology
  • Prostatic Neoplasms / drug therapy*
  • Prostatic Neoplasms / metabolism
  • Prostatic Neoplasms / pathology
  • T-Lymphocytes / metabolism*


  • Antifreeze Proteins
  • Antigens, Tumor-Associated, Carbohydrate
  • Antineoplastic Agents
  • Fish Proteins
  • Galectin 3
  • Neoplasm Proteins
  • Thomsen-Friedenreich antigen