Over-expression of urokinase receptor in human epidermoid-carcinoma cell line (HEp3) increases tumorigenicity on chorio-allantoic membrane and in severe-combined-immunodeficient mice
✍ Scribed by Mi-Ae Lyu; Yang-Kyu Choi; Bo-Na Park; Byung-Joo Park; Bum-Joon Kim; Il-Kyoo Park; Byung-Hwa Hyun; Yoon-Hoh Kook
- Publisher
- John Wiley and Sons
- Year
- 1998
- Tongue
- French
- Weight
- 323 KB
- Volume
- 77
- Category
- Article
- ISSN
- 0020-7136
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✦ Synopsis
Using chorio-allantoic membranes (CAMs) of chick embryos and severe-combined-immunodeficient (SCID) mice, we investigated the effects of urokinase-type plasminogenactivator 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-overexpressing clones formed larger tumors (G40 mm 3 ) than did parent HEp3 cells on CAMs. Moreover, when the u-PAR-overexpressing 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.