title: Inhibition of human tumor xenograft growth in nude mice by a novel monoclonal anti-HSPG isolated from human liver.
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.
authors.affiliation: 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
authors.forename: Preeyanat
authors.initials: P
authors.lastname: Vongchan
authors.forename: Suchart
authors.initials: S
authors.lastname: Kothan
authors.forename: Yupanan
authors.initials: Y
authors.lastname: Wutti-In
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Linhardt
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000737:chemistry; D017209:Apoptosis; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D056945:Hep G2 Cells; D019812:Heparan Sulfate Proteoglycans / Q000276:immunology*; D006801:Humans; D007150:Immunohistochemistry / Q000379:methods; D007167:Immunotherapy / Q000379:methods; D008099:Liver / Q000378:metabolism* / Q000473:pathology; D008113:Liver Neoplasms / Q000378:metabolism / Q000628:therapy*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D011509:Proteoglycans / Q000737:chemistry; D013778:Tetrazolium Salts / Q000494:pharmacology; D013844:Thiazoles / Q000494:pharmacology
chemical_list: D000911:Antibodies, Monoclonal; D019812:Heparan Sulfate Proteoglycans; D011509:Proteoglycans; D013778:Tetrazolium Salts; D013844:Thiazoles; C022616:thiazolyl blue