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Co‐expression of urokinase‐type plasminogen activator and its receptor in human gastric‐cancer cell lines correlates with their invasiveness and tumorigenicity
Author(s) -
Park IlKyoo,
Kim BumJoon,
Goh YoungJoo,
Lyu MiAe,
Park ChungGyu,
Hwang and EungSoo,
Kook YoonHoh
Publication year - 1997
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/(sici)1097-0215(19970529)71:5<867::aid-ijc27>3.0.co;2-3
Subject(s) - plasminogen activator , urokinase receptor , cell culture , biology , cancer research , receptor , cell , chorioallantoic membrane , cancer cell , plasmin , collagenase , metalloproteinase , cancer , matrix metalloproteinase , urokinase , microbiology and biotechnology , pathology , endocrinology , medicine , angiogenesis , enzyme , biochemistry , genetics
The expression of urokinase‐type plasminogen activator (u‐PA), its receptor (u‐PAR) and metalloproteases activity were analyzed in 4 human gastric‐cancer cell lines (AGS, Hs746T, SNU‐1, and SNU‐5), in an attempt to relate these activities to their invasive potential and tumorigenicity on the modified chorioallantoic membranes (CAM) of chick embryos. Only 1 of the 4 cell lines tested, Hs746T, expressed both u‐PA and u‐PAR as well as MMP‐2, but not MMP‐9. This cell line was both tumorigenic and highly invasive (51.3 ± 13.1%) on a modified CAM. Its invasive capacity was comparable with that of a highly malignant human epidermoid‐carcinoma cell line (HEp3), which usually showed 40 to 50% invasiveness. The 3 other cell lines all produced MMP‐2 and MMP‐9, but only AGS showed moderate invasiveness (24.2 ± 8.8%). While antibodies to u‐PA were significantly effective in reducing CAM invasiveness of Hs746T cells by approximately 40%, the invasiveness of the t‐PA‐expressing AGS cell line was not affected by anti‐t‐PA antibodies. These results suggest that when one of the components of the u‐PA/u‐PAR system (the enzyme and/or the receptor) is not produced and u‐PA/u‐PAR‐dependent cell‐surface proteolytic activity is thereby diminished, the malignant phenotype that can be determined by tumorigenicity and invasion of connective tissue on a CAM is compromised. Production of both type‐IV collagenases (MMP‐2 and MMP‐9) cannot offset this deficiency. Int. J. Cancer 71: 867‐873, 1997. © 1997 Wiley‐Liss Inc.