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


Guha P., Kaptan E. , Bandyopadhyaya G., Kaczanowska S., Davila E., Thompson K., ...More

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, vol.110, no.13, pp.5052-5057, 2013 (Journal Indexed in SCI) identifier identifier identifier

  • Publication Type: Article / Article
  • Volume: 110 Issue: 13
  • Publication Date: 2013
  • Doi Number: 10.1073/pnas.1202653110
  • Title of Journal : PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
  • Page Numbers: pp.5052-5057
  • Keywords: antifreeze glycoprotein, PC3-luciferase cells, galectin-3 knockout PC3-luciferase cells, TF antigen, surface plasmon resonance, POSITIVE COOPERATIVITY, BREAST-CANCER, ENDOTHELIUM, RECOGNITION, PROGRESSION, EXPRESSION, MECHANISM, ADHESION, ANTIGEN, LECTIN

Abstract

Cancer metastasis and immune suppression are critical issues in cancer therapy. Here, we show that a beta-galactoside-binding lectin [galectin-3 (gal3)] that recognizes the Thomsen-Friedenreich disaccharide (TFD, Gal beta 1,3GalNAc) 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 anti-metastatic agent for the treatment of various cancers, including prostate adenocarcinoma.