Plant Lectins Targeting O-Glycans at the Cell Surface as Tools for Cancer Diagnosis, Prognosis and Therapy

Abstract

Aberrant O-glycans expressed at the surface of cancer cells consist of membrane-tethered glycoproteins (T and Tn antigens) and glycolipids (Lewis a, Lewis x and Forssman antigens). All of these O-glycans have been identified as glyco-markers of interest for the diagnosis and the prognosis of cancer diseases. These epitopes are specifically detected using T/Tn-specific lectins isolated from various plants such as jacalin from Artocarpus integrifola, and fungi such as the Agaricus bisporus lectin. These lectins accommodate T/Tn antigens at the monosaccharide-binding site; residues located in the surrounding extended binding-site of the lectins often participate in the binding of more extended epitopes. Depending on the shape and size of the extended carbohydrate-binding site, their fine sugar-binding specificity towards complex O-glycans readily differs from one lectin to another, resulting in a great diversity in their sugar-recognition capacity. T/Tn-specific lectins have been extensively used for the histochemical detection of cancer cells in biopsies and for the follow up of the cancer progression and evolution. T/Tn-specific lectins also induce a caspase-dependent apoptosis in cancer cells, often associated with a more or less severe inhibition of proliferation. Moreover, they provide another potential source of molecules adapted to the building of photosensitizer-conjugates allowing a specific targeting to cancer cells, for the photodynamic treatment of tumors.

A mitogenic lectin from Rhizoctonia bataticola arrests growth, inhibits metastasis, and induces apoptosis in human colon epithelial cancer cells

“…RBL inhibits the viability of these cells both in time and dose dependent manner following its binding to the cell surface. The growth inhibitory effect of lectins on various cancer cell lines has been reported …”

“…The growth inhibitory effect of lectins on various cancer cell lines has been reported. 31,32 FIGURE 7 RBL inhibits metastasis of SW620 cells: RBL inhibits SW620 cell adhesion: Adhesion assay of SW620 cells pre-incubated with RBL was performed using 96-well plates coated with collagen (20 and 40 µg/mL) and fibronectin (10 and 20 μg/mL) for 2 h. Cells adhered were photographed (A2) and quantified by MTT assay (A and A1). Cell adhesion was calculated as a percentage of adhesion compared to control.…”

Efficacy studies of Sclerotium rolfsii lectin on breast cancer using NOD SCID mouse model

“…To date, there are reports on some lectins with anticancer properties demonstrated by in vitro and in vivo studies such as lectins from Viscum album , Agaricus bisporus , Agrocybe aegerita , Ricinus communis , and Arachis hypogaea . However, very few of them have reached to clinical trials such as a lectin from Viscum album , and Mistletoe lectin has cleared clinical studies and is being used as complementary therapy in Europe .…”

Plant Lectins with Insecticidal and Insectistatic Activities

“…The lectins could be a good biotechnological alternative in the control of bacterial biofilms for different purposes, for example, clinical applications [61]. In general, plant lectins have been widely used for studying carbohydrates on cell surface, for typing blood groups, isolating glycoconjugates, and detecting changes in normal oligosaccharide synthesis in tumoral disorders and other pathologies [62][63][64][65][66].…”