title: Overexpression of urokinase-type plasminogen activator in human gastric cancer cell line (AGS) induces tumorigenicity in severe combined immunodeficient mice.
abstract: The significance of urokinase-type plasminogen activator (uPA) expression in gastric cancer development was tested by using a human uPA cDNA transfection approach and an in vivo severe combined immunodeficient (SCID) mouse model. The AGS gastric cancer cell line, which has urokinase-type plasminogen-activator receptor (uPAR) but lacks uPA, was transfected with a plasmid containing human uPA cDNA and injected into the backs of SCID mice. Compared with the parent AGS cells, uPA protein secretion in AGS-2-, AGS-4-, and AGS-8-transfected cells increased by 26.1-, 34.6-, and 4.8-fold, respectively (P < 0.05). mRNA expression levels of uPA in the AGS-4 clone were much stronger than those in AGS-2 and AGS-8 clones. After the cancer cells (2 x 10(6)) were injected s.c. into the SCID mice, a palpable mass was observed at the injection site at around 140 days post-injection, followed by accelerated growth of the xenograft up to 180 days post-injection only in the high uPA-producing clone (AGS-4). These results suggest that continuous and high production of uPA by tumor cells is one of the important factors reflecting the malignancy of gastric cancer cells.
authors.affiliation: Korea Research Institute of Bioscience and Biotechnology, Taejon, 305-333, Korea.
authors.forename: Yang-Kyu
authors.initials: YK
authors.lastname: Choi
authors.forename: Byung-Il
authors.initials: BI
authors.lastname: Yoon
authors.forename: Yoon-Hoh
authors.initials: YH
authors.lastname: Kook
authors.forename: Young-Suk
authors.initials: YS
authors.lastname: Won
authors.forename: Jin-Hyun
authors.initials: JH
authors.lastname: Kim
authors.forename: Chul-Ho
authors.initials: CH
authors.lastname: Lee
authors.forename: Byung-Hwa
authors.initials: BH
authors.lastname: Hyun
authors.forename: Goo-Taeg
authors.initials: GT
authors.lastname: Oh
authors.forename: John
authors.initials: J
authors.lastname: Sipley
authors.forename: Dae-Yong
authors.initials: DY
authors.lastname: Kim
mesh_terms: D000818:Animals; D006801:Humans; D007150:Immunohistochemistry; D051379:Mice; D016513:Mice, SCID; D013274:Stomach Neoplasms / Q000201:enzymology* / Q000473:pathology; D014162:Transfection; D014407:Tumor Cells, Cultured; D014568:Urokinase-Type Plasminogen Activator / Q000032:analysis / Q000096:biosynthesis*
chemical_list: D014568:Urokinase-Type Plasminogen Activator