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., ...Daha Fazla

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, cilt.110, sa.13, ss.5052-5057, 2013 (SCI-Expanded) identifier identifier identifier

  • Yayın Türü: Makale / Tam Makale
  • Cilt numarası: 110 Sayı: 13
  • Basım Tarihi: 2013
  • Doi Numarası: 10.1073/pnas.1202653110
  • Dergi Adı: PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
  • Derginin Tarandığı İndeksler: Science Citation Index Expanded (SCI-EXPANDED), Scopus
  • Sayfa Sayıları: ss.5052-5057
  • Anahtar Kelimeler: 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
  • İstanbul Üniversitesi Adresli: Evet

Özet

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.