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Inhibition of human tumor xenograft growth in nude mice by a novel monoclonal anti-HSPG isolated from human liver
Authors:Vongchan Preeyanat  Kothan Suchart  Wutti-In Yupanan  Linhardt Robert J
Institution:Division of Transfusion Science, Department of Medical Technology, Faculty of Associated Medical Science, CMU, 110 Inthawaroros Road, Suthep, Muang, Chiang Mai 50200, Thailand. preyanat@chiangmai.ac.th
Abstract:Heparan sulfate proteoglycans (HSPGs) were isolated from normal human liver and α monoclonal antibody (MAb) was raised against them. Preliminary studies showed that MAb clone 1E4-1C2 was able to react with many cell lines tested, including hematopoietic cells and solid tumors. MAb1E4-1C2 was used to study whether HSPG was involved in growth and proliferation of human liver cancer using hepatocellular carcinoma (HCC) cell line (HepG2) as a model. Inhibition by MAb1E4-1C2 of HepG2 cell proliferation was studied in vitro by MTT assay. For in vivo assay, xenograft induction in athymic mice was performed. The results showed that MAb1E4-1C2 inhibited proliferation of HepG2 cells significantly, compared to isotype and medium control. MAb1E4-1C2 also suppressed the growth of tumor, resulting in smaller tumor size and weight. The investigation also showed that MAb1E4-1C2 inhibited proliferation and restricted tumor growth through the induction of apoptosis. The results suggest that HSPG might be involved in liver cancer cell proliferation. Therefore, a specific MAb that was raised against liver HSPG might be an alternative therapeutic agent for the treatment of human liver cancer.
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