Exquisite specificity of mitogenic lectin from Cephalosporium curvulum to core fucosylated N-glycans

Abstract

Lectins are carbohydrate binding proteins that are gaining attention as important tools for the identification of specific glycan markers expressed during different stages of the cancer. We earlier reported the purification of a mitogenic lectin from human pathogenic fungus Cephalosporium curvulum (CSL) that has complex sugar specificity when analysed by hapten inhibition assay. In the present study, we report the fine sugar specificity of CSL as determined by glycan array analysis. The results revealed that CSL has exquisite specificity towards core fucosylated N-glycans. Fucosylated trimannosyl core is the basic structure required for the binding of CSL. The presence of fucose in the side chain further enhances the avidity of CSL towards such glycans. The affinity of CSL is drastically reduced towards the non-core fucosylated glycans, in spite of their side chain fucosylation. CSL showed no binding to the tested O-glycans and monosaccharides. These observations suggest the unique specificity of CSL towards core fucosylated N-glycans, which was further validated by binding of CSL to human colon cancer epithelial and hepatocarcinoma cell lines namely HT29 and HepG2, respectively, that are known to express core fucosylated N-glycans, using AOL and LCA as positive controls. LCA and AOL are fucose specific lectins that are currently being used clinically for the diagnosis of hepatocellular carcinomas. Most of the gastrointestinal markers express core fucosylated N-glycans. The high affinity and exclusive specificity of CSL towards α1-6 linkage of core fucosylated glycans compared to other fucose specific lectins, makes it a promising molecule that needs to be further explored for its application in the diagnosis of gastrointestinal cancer.

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

“…RBL which shows differential binding to primary and metastatic human colon cancer tissues compared to normal tissues indicates that RBL has the ability to recognize and bind to tumor specific glycans selectively expressed on human colon cancer tissues and hence has promising potential as diagnostic tool. In this context, RBL resembles some of the lectins reported like Pholiota squarrosa lectin ( PhoSL ) and Aleuria aurantia lectin (AAL), Cephalosporium curvulum lectin (CSL), and Aspergillus oryzae lectin (AOL) . Binding of RBL to human colon cancer cells was also demonstrated by flowcytometry which showed its strong binding to all the three cells, HT 29, SW480, and SW620 which can be effectively blocked by a glycoprotein, asialofetuin expressing N‐glycans.…”

“…In this context, RBL resembles some of the lectins reported like Pholiota squarrosa lectin (PhoSL) and Aleuria aurantia lectin (AAL), Cephalosporium curvulum lectin (CSL), and Aspergillus oryzae lectin (AOL). 29,30 Binding of RBL to human colon cancer cells was also demonstrated by flowcytometry which showed its strong binding to all the three cells, HT 29, SW480, and SW620 which can be effectively blocked by a glycoprotein, asialofetuin expressing N-glycans. The binding of RBL directly correlates with the high expression of different type of N glycans reported in these colon cancer cell lines 16 and also it shows that RBL binding is glycan mediated.…”

Exploration of carbohydrate binding behavior and anti-proliferative activities of Arisaema tortuosum lectin

“…Fucosyltransferase enzyme gene responsible for core fucosylation of N -glycans is upregulated in various carcinomas [30]. Expression of fucosylated N -glycans has been reported to be associated with the events of transformation in hepatoma and cancers related to digestive tract [10, 31]. This has encouraged the application of fucosylated N -glycans as markers for respective cancers.…”

“…These variations can explain the differential binding of ATL to different cancer cells and hence diversity in its anti-proliferative potential. It is well known that plant lectins mediate their anti-proliferative properties due to their capability to bind to foreign glycans [7, 10]. Thus a lack of receptors for ATL on the surface of A498 cells could explain the non-responsiveness of the latter towards the treatment of former.…”

“…This is due to their highly specific binding nature which remains central to their various activities. Owing to this, lectins are known to bind directly to specific cells [10].…”