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Over‐expression of urokinase receptor in human epidermoid‐carcinoma cell line (HEp3) increases tumorigenicity on chorio‐allantoic membrane and in severe‐combined‐immunodeficient mice
Author(s) -
Lyu MiAe,
Choi YangKyu,
Park BoNa,
Park ByungJoo,
Kim BumJoon,
Park IlKyoo,
Hyun ByungHwa,
Kook YoonHoh
Publication year - 1998
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(19980717)77:2<257::aid-ijc15>3.0.co;2-8
Subject(s) - biology , plasminogen activator , clone (java method) , urokinase receptor , cell culture , epidermoid carcinoma , microbiology and biotechnology , transfection , immunohistochemistry , cancer research , urokinase , pathology , cancer , immunology , gene , endocrinology , medicine , biochemistry , genetics
Using chorio‐allantoic membranes (CAMs) of chick embryos and severe‐combined‐immunodeficient (SCID) mice, we investigated the effects of urokinase‐type plasminogen‐activator receptor (u‐PAR) over‐expression on the process of invasion and tumorigenicity. By the transfection of u‐PAR cDNA, 3 u‐PAR‐over‐expressing clones expressing 1.6‐ to 4.6‐fold more u‐PAR mRNA than parent cells were obtained from a human epidermoid‐carcinoma cell line, HEp3, that expresses urokinase‐type plasminogen activator (u‐PA) and u‐PAR. All the u‐PAR‐over‐expressing clones showed greater invasiveness (13 to 29%) than that of parent HEp3 cells on CAMs. Immunohistochemistry revealed densely stained u‐PAR‐positive cells near the margin of the tumor, where a u‐PAR‐over‐expressing clone, designated SM‐3, was invading thickened fibrous tissue on CAMs. Three u‐PAR‐over‐expressing clones formed larger tumors (>40 mm 3 ) than did parent HEp3 cells on CAMs. Moreover, when the u‐PAR‐over‐expressing clone (SM‐3) was injected s.c. into the back of the SCID mice it produced a larger tumor volume than the control (HEp3) and down‐regulated (AS‐2) clones and significantly shortened the survival of SCID mice. These results demonstrate that increased u‐PAR expression is an important factor in determining the malignant phenotype that makes cancer cells more invasive and tumorigenic. Int. J. Cancer 77:257–263, 1998.© 1998 Wiley‐Liss, Inc.