Monoclonal antibody (5F3) defining renal cell carcinoma-associated antigen disialosyl globopentaosylceramide (V3NeuAcIV6NeuAcGb5), and distribution pattern of the antigen in tumor and normal tissues |
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Authors: | Ito A Saito S Masuko T Oh-Eda M Matsuura T Satoh M Nejad F M Enomoto T Orikasa S Hakomori S I |
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Institution: | (1) Department of Urology, Tohoku University, School of Medicine, 1-1 Seiryo-machi, Aoba-ku, Sendai, 980-8574, Japan;(2) Molecular Cell Biology Laboratory, Graduate School of Pharmaceutical Science, Tohoku University, Sendai, 980-8578, Japan;(3) Pacific Northwest Research Institute, 720 Broadway, Seattle, WA, 98122-4327;(4) Departments of Pathobiology and Microbiology, University of Washington, Seattle, WA 98195, USA;(5) Fuji-Gotemba Research Lab, Chugai Pharmaceutical Co., Ltd, Gotemba, 412-8513, Japan |
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Abstract: | Renal cell carcinoma (RCC) has been characterized by high expression of three types of disialogangliosides: two based on lacto-series type 1 structure (disialosyl Lc4, GalNAc disialosyl Lc4), the other based on globo-series structure (disialosyl globopentaosylceramide; disialosyl Gb5). The present study established a mAb, 5F3, directed to disialosyl Gb5. 5F3 was established after immunization with RCC cell line ACHN. The major disialoganglioside antigen isolated from ACHN cells, showing specific reactivity with 5F3, was characterized unequivocally as disialosyl Gb5 (V3NeuAcIV6NeuAcGb5) by identification of the core structure as globopentaosylceramide (Gb5) after enzymatic and acid hydrolysis, and by 2-dimensional 1H-NMR spectroscopy. 5F3 does not react with monosialosyl Gb5 (V3NeuAcGb5), Gb5, or any lacto-series structures. 5F3 strongly stained 19 of 41 cases of primary RCC tissue. It reacted with proximal tubules (but not distal tubules) of kidney, microglial cells of cerebrum and cerebellum, goblet cells of stomach and intestine, smooth muscle of various organs. It did not react with parenchymatous cells of various organs, except for kidney epithelia and prostate stroma. Immunostaining of RCC tissue by mAb 5F3, in combination with staining by other antibodies directed to globo-series and lacto-series structures, has prognostic significance in defining metastatic potential of RCC. |
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Keywords: | disialoganglioside globo-series monoclonal antibody 5F3 metastasis renal cell carcinoma |
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