Abstract
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 mm3) 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.
Original language | English (US) |
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Pages (from-to) | 257-263 |
Number of pages | 7 |
Journal | International journal of cancer |
Volume | 77 |
Issue number | 2 |
DOIs | |
State | Published - 1998 |
Externally published | Yes |
ASJC Scopus subject areas
- Oncology
- Cancer Research