Cancer discrimination by on-cell N-glycan ligation

Abstract

In the field of molecular imaging, selectivity for target cells is a key determinant of the degree of imaging contrast. Previously, we developed a pre-targeted method by which target cells could be selectively imaged using a labeled N-glycan that was ligated in situ with an integrintargeted cyclic RGD peptide on the cell surface. Here we demonstrate the power of our method in discriminating various cancerous and non-cancerous cells that cannot be distinguished using conventional RGD ligands. Using four cyclic RGDyK peptides with various linker lengths with five N-glycans, we identify optimal combinations to discriminate six types of α v β 3 integrin-expressing cells on 96-well plates. The optimal combinations of RGD and Nglycan ligands for the target cells are fingerprinted on the plates, and then used to selectively image tumors in xenografted mouse models. Using this method, various N-glycan molecules, even those with millimolar affinities for their cognate lectins, could be used for selective cancer cell differentiation.

Glycosylation in Cervical Cancer: New Insights and Clinical Implications

“…The sialylation changes of cell surface adherent receptor integrin b4 during the TGF-b-induced EMT process are further proved at the protein level using proteomic analysis (62). The integrin family involves various glycan-based posttranslational modifications that mediate cell-extracellular matrix (ECM) and cell-cell adhesions in cervical cancer cells and other types of cancer cells (121).…”

“…Because many of these glycan-binding proteins have diverse roles in cancer, alterations in glycosylation are likely to have a novel role in the cervical cancer field (62). In the field of cancer cell labeling, molecular imaging using labeled N-glycans has become a powerful method of selective discrimination between cancerous and non-cancerous cells (121). Although much attention has been paid to sialylation and fucosylation levels on cancer cell surface analyzed by lectin blot and enzyme-linked lectin assay programs, recent advances in high-throughput technologies such as glycan-based arrays and microbead-based immunoassays expand a great diagnostic potential for clinical diagnosis in cervical cancer (4,62).…”