Open AccessOverexpression of Urokinase‐type Plasminogen Activator in Human Gastric Cancer Cell Line (AGS) Induces Tumorigenicity in Severe Combined Immunodeficient Mice
Author(s) -
Choi YangKyu,
Yoon ByungIl,
Kook YoonHoh,
Won YoungSuk,
Kim JinHyun,
Lee ChulHo,
Hyun ByungHwa,
Oh GooTaeg,
Sipley John,
Kim DaeYong
Publication year - 2002
Publication title -
japanese journal of cancer research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.035
H-Index - 141
eISSN - 1349-7006
pISSN - 0910-5050
DOI - 10.1111/j.1349-7006.2002.tb01253.x
Subject(s) - urokinase receptor , plasminogen activator , transfection , cancer research , clone (java method) , cell culture , urokinase , microbiology and biotechnology , biology , cancer cell , severe combined immunodeficiency , cancer , in vivo , medicine , endocrinology , gene , biochemistry , genetics
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 ( Pr <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×l0 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.