The human tissue kallikrein family of serine proteases (hK1-hK15 encoded by the 
genes KLK1-KLK15) is involved in several cancer-related processes. Accumulating 
evidence suggests that certain tissue kallikreins are part of an enzymatic 
cascade pathway that is activated in ovarian cancer and other malignant 
diseases. In the present study, OV-MZ-6 ovarian cancer cells were stably 
co-transfected with plasmids expressing hK4, hK5, hK6, and hK7. These cells 
displayed similar proliferative capacity as the vector-transfected control cells 
(which do not express any of the four tissue kallikreins), but showed 
significantly increased invasive behavior in an in vitro Matrigel invasion assay 
(p<0.01; Mann-Whitney U-test). For in vivo analysis, the cancer cells were 
inoculated into the peritoneum of nude mice. Simultaneous expression of hK4, 
hK5, hK6, and hK7 resulted in a remarkable 92% mean increase in tumor burden 
compared to the vector-control cell line. Five out of 14 mice in the 'tissue 
kallikrein overexpressing' group displayed a tumor/situs ratio greater than 
0.198, while this weight limit was not exceeded at all in the vector control 
group consisting of 13 mice (p=0.017; chi2 test). Our results strongly support 
the view that tumor-associated overexpression of tissue kallikreins contributes 
to ovarian cancer progression.