Correlative fine specificity of several Thomsen-Friedenreich disaccharide-binding proteins with an effect on tumor cell proliferation

Fernando J. Irazoqui, Bo Jansson, Pablo H.H. Lopez, Gustavo A. Nores

Research output: Contribution to journalArticle

Abstract

Epithelial cancer cells show increased cell surface expression of mucin antigens with aberrant O-glycosylation, notably type I core (Galβ1-3GalNAcα), termed Thomsen-Friedenreich disaccharide (TFD), a chemically well-defined carbohydrate antigen with a proven link to malignancy. Several TFD-binding proteins influence the proliferation of cells to which they bind. We studied the fine specificity of TFD-binding proteins and its relationship with epithelial tumor cell proliferation. Competitive binding assays against asialoglycophorin showed that Agaricus bisporus lectin (ABL) and human anti-TFD monoclonal antibody (mAb) TF1 were inhibited only by TFD and its α-derivatives. Peanut agglutinin (PNA), mAb TF2, and mAb TF5 were also inhibited by other carbohydrates such as lacto-N-biose (Galβ1-3GlcNAc), lactose, and (Meα or β) Gal, indicating lower recognition of the axial C-4 hydroxyl group position of GalNAc from TFD, and the major relevance of the terminal Gal on interaction of these three TFD-binding proteins. In the direct glycolipid-binding assay, ABL bound mostly to α-anomeric TFD-bearing glycolipids, whereas PNA interacted mainly with β-linked TFD. Of the three anti-TFD mAbs analyzed, all bound N5b (terminal β-TFD), but only TF2 interacted with N6 (terminal α-TFD). These findings indicate that TFD-binding proteins that stimulate the proliferation of epithelial tumor cell lines recognize mainly a terminal β-Gal region of β-linked TFD, whereas ABL, which inhibits the proliferation of these tumor cells, binds mainly to subterminal GalNAc of α-anomeric TFD.

Original languageEnglish (US)
Pages (from-to)33-37
Number of pages5
JournalJournal of biochemistry
Volume130
Issue number1
DOIs
StatePublished - Jan 1 2001
Externally publishedYes

Keywords

  • Carbohydrate-binding proteins
  • Cell proliferation
  • Thomsen-Friedenreich disaccharide

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology

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