title: Cod glycopeptide with picomolar affinity to galectin-3 suppresses T-cell apoptosis and prostate cancer metastasis.
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.
authors.affiliation: Department of Biochemistry and Molecular Biology, Institute of Marine and Environmental Technology, University of Maryland School of Medicine, Baltimore, MD 21201, USA.
authors.forename: Prasun
authors.initials: P
authors.lastname: Guha
authors.forename: Engin
authors.initials: E
authors.lastname: Kaptan
authors.forename: Gargi
authors.initials: G
authors.lastname: Bandyopadhyaya
authors.forename: Sabina
authors.initials: S
authors.lastname: Kaczanowska
authors.forename: Eduardo
authors.initials: E
authors.lastname: Davila
authors.forename: Keyata
authors.initials: K
authors.lastname: Thompson
authors.forename: Stuart S
authors.initials: SS
authors.lastname: Martin
authors.forename: Dhananjaya V
authors.initials: DV
authors.lastname: Kalvakolanu
authors.forename: Gerardo R
authors.initials: GR
authors.lastname: Vasta
authors.forename: Hafiz
authors.initials: H
authors.lastname: Ahmed
mesh_terms: D000230:Adenocarcinoma / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D000818:Animals; D021301:Antifreeze Proteins / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D015295:Antigens, Tumor-Associated, Carbohydrate / Q000737:chemistry / Q000378:metabolism; D000970:Antineoplastic Agents / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D029941:Fish Proteins / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D048389:Gadus morhua; D037502:Galectin 3 / Q000378:metabolism*; D061307:Human Umbilical Vein Endothelial Cells; D006801:Humans; D019169:Jurkat Cells; D008297:Male; D051379:Mice; D009362:Neoplasm Metastasis; D009363:Neoplasm Proteins / Q000378:metabolism*; D009389:Neovascularization, Pathologic / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D011471:Prostatic Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D013601:T-Lymphocytes / Q000378:metabolism*
chemical_list: D021301:Antifreeze Proteins; D015295:Antigens, Tumor-Associated, Carbohydrate; D000970:Antineoplastic Agents; D029941:Fish Proteins; D037502:Galectin 3; D009363:Neoplasm Proteins; C016467:Thomsen-Friedenreich antigen