Over-expression of urokinase receptor in human epidermoid-carcinoma cell line (HEp3) increases tumorigenicity on chorio-allantoic membrane and in severe-combined-immunodeficient mice.
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-overexpressing clones formed larger tumors (>40 mm3) 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.
Lyu
M A
MA
Department of Microbiology and Cancer Research Center, Seoul National University College of Medicine, Republic of Korea.
Choi
Y K
YK
Park
B N
BN
Kim
B J
BJ
Park
I K
IK
Hyun
B H
BH
Kook
Y H
YH
D000482:Allantois; D000818:Animals; D002294:Carcinoma, Squamous Cell / Q000378:metabolism*; D002642:Chick Embryo; D002823:Chorion; D006801:Humans; D051379:Mice; D016513:Mice, SCID; D009361:Neoplasm Invasiveness; D009362:Neoplasm Metastasis; D017395:Plasminogen Activator Inhibitor 1 / Q000378:metabolism; D011956:Receptors, Cell Surface / Q000378:metabolism*; D055293:Receptors, Urokinase Plasminogen Activator; D014162:Transfection; D014407:Tumor Cells, Cultured; D014568:Urokinase-Type Plasminogen Activator / Q000378:metabolism
C524898:PLAUR protein, human; D017395:Plasminogen Activator Inhibitor 1; C524899:Plaur protein, mouse; D011956:Receptors, Cell Surface; D055293:Receptors, Urokinase Plasminogen Activator; D014568:Urokinase-Type Plasminogen Activator