ganglioside--gd2 and Adenocarcinoma

Using flow cytometry GD2 ganglioside expression was evaluated both on colorectal adenocarcinoma cell lines and on tumor tissue samples from colorectal cancer patients. The marker was found on EpCAM-positive tumor cells in 6 of 12 patients' samples but not on the HT29 and CaCo-2 cell lines. GD2 expression was not an exceptional feature of cancer stem cells, since its expression level was similar on CD133-positive and CD133-negative tumor cells. Thus, the presence of GD2 ganglioside was revealed on colorectal adenocarcinoma cells for the first time. This finding makes it possible to use targeted therapy to treat this disease.. Metodom protochnoĭ tsitometrii issledovana ékspressiia gangliozida GD2 na kletkakh liniĭ kolorektal'noĭ adenokartsinomy HT29 i CaCo-2, a takzhe na obraztsakh opukholevoĭ tkani ot bol'nykh kolorektal'nym rakom. Issleduemyĭ marker fakticheski otsutstvoval na kletochnykh liniiakh, no ékspressirovalsia na EpCAM-pozitivnykh opukholevykh kletkakh u 6 iz 12 patsientov. Ékspressiia GD2 ne byla assotsiirovana s subpopuliatsieĭ rakovykh stvolovykh kletok, poskol'ku uroven' ego ékspressii ne otlichalsia na CD133-pozitivnykh i CD133-negativnykh kletkakh. Takim obrazom, vpervye vyiavleno prisutstvie gangliozida GD2 na kletkakh kolorektal'noĭ adenokartsinomy, chto otkryvaet vozmozhnost' ispol'zovaniia targetnoĭ terapii dlia lecheniia étogo zabolevaniia.

Topics: Adenocarcinoma; Caco-2 Cells; Colorectal Neoplasms; Gangliosides; HT29 Cells; Humans

Human melanoma cells express relatively large amounts of the disialogangliosides GD3 and GD2 on their surface whereas neuroblastoma cells express GD2 as a major ganglioside. Monoclonal antibodies (Mabs) directed specifically to the carbohydrate moiety of GD3 and GD2 inhibit melanoma and neuroblastoma cell attachment to various substrate adhesive proteins, e.g. collagen, vitronectin, laminin, fibronectin, and a heptapeptide, glycyl-L-arginyl-glycyl-L-aspartyl-L-seryl-L-prolyl-L-cysteine, which constitutes the cell attachment site of fibronectin. Cells that are preattached to a fibronectin substrate can also be induced to detach and round up in the presence of purified anti-ganglioside Mab. Moreover, when melanoma cells that contain both GD2 and GD3 are incubated with Mabs directed to both of these molecules an additive inhibition is observed. The specificity of this inhibition is demonstrated since Mabs of various isotypes directed to either protein or carbohydrate epitopes on a number of other major melanoma or neuroblastoma cell surface antigens have no effect on cell attachment. A study of the kinetics involved in this inhibition indicates that significant effects occur during the first 5 min of cell attachment, suggesting an important role for GD2 and GD3 in the initial events of cell-substrate interactions. The role of gangliosides in cell attachment apparently does not directly involve a strong interaction with fibronectin since we could not observe any binding of radiolabeled fibronectin or fragments of the molecule known to contain the cell attachment site to melanoma gangliosides separated on thin-layer chromatograms. An alternative explanation would be that gangliosides may play a role in the electrostatic requirements for cell-substrate interactions. In this regard, controlled periodate oxidation of terminal, unsubstituted sialic acid residues on the cell surface not only specifically destroys the antigenic epitopes on GD2 and GD3 recognized by specific Mabs but also inhibits melanoma cell and neuroblastoma cell attachment. In fact, the periodate-induced ganglioside oxidation and the inhibition of cell attachment are equally dose dependent. These data suggest that cell-substratum interactions may depend in part on the electrostatic environment provided by terminal sialic acid residues of cell surface gangliosides and possibly other anionic glycoconjugates.

Topics: Adenocarcinoma; Antibodies, Monoclonal; Antigens, Surface; Cell Adhesion; Cell Line; Extracellular Matrix; Fibronectins; Gangliosides; Humans; Laminin; Lung Neoplasms; Melanoma; Neuroblastoma; Periodic Acid