Overexpression of the human tissue kallikrein genes KLK4, 5, 6, and 7 increases the malignant phenotype of ovarian cancer cells

• DOI: 10.1515/bc.2006.102
• Publication Date: 2006-06-26T14:42:27Z
• Authors: Panagiotis Prezas; Matthias J.E. Arlt; Petar Viktorov; Antoninus Soosaip...; Leon Holzscheiter; Manfred Schmitt; Maroulio Talieri; Eleftherios P. Di...; Achim Krüger; Viktor Magdolen
• Keywords: Ovarian Neoplasms; Transplantation, Heterologous; Mice, Nude; Neoplasms, Experimental; Tumor Burden; 3. Good health; Gene Expression Regulation, Neoplastic; Mice; 03 medical and health sciences; 0302 clinical medicine; Cell Line, Tumor; Animals; Humans; Female; Kallikreins; Neoplasm Invasiveness; Tissue Kallikreins; Cell Proliferation

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