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

Prasun Guha, Engin Kaptan, Gargi Bandyopadhyaya, Sabina Kaczanowska, Eduardo Davila, Keyata Thompson, Stuart S. Martin, Dhananjaya V. Kalvakolanu, Gerardo R. Vasta, Hafiz Ahmed

Research output: Contribution to journalArticlepeer-review

Abstract

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.

Original languageEnglish (US)
Pages (from-to)5052-5057
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume110
Issue number13
DOIs
StatePublished - Mar 26 2013
Externally publishedYes

Keywords

  • Antifreeze glycoprotein
  • Galectin-3 knockout PC3-luciferase cells
  • PC3-luciferase cells
  • Surface plasmon resonance
  • TF antigen

ASJC Scopus subject areas

  • General

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