Genetic reduction of matriptase-1 expression is associated with a reduction in the aggressive phenotype of prostate cancer cells in vitro and in vivo
Andrew J Sanders, Christian Parr, Gaynor Davies, Tracey A Martin, Jane Lane, Malcolm D Mason, and Wen G Jiang
Purpose: Matriptase-1 has been implicated as playing an important role in various types of cancer progression through many different cancer related pathways. In the current study we assessed the efficacy of targeting matriptase-1 using ribozyme technology in vitro and in vivo. Experimental Design: Matriptase-1 expression was reduced in the PC-3 and DU-145 cell line using hammer-head ribozyme transgenes. In vitro assays were set up to assess changes in growth, invasion, adhesion and migration in these cells. In vivo tumour development model was also used to examine the efficacy of targeting matriptase-1 in a living environment. Results: The in vitro results suggest an overall reduction in the aggressive nature of the two cell lines (PC-3 and DU-145) when matriptase-1 levels are reduced, with properties such as growth, invasiveness and migration all being reduced (in most cases a greater than 50% reduction in migration and invasion compared to the control was observed), though strangely an increase in adhesion is seen in the PC-3 knockout. The in vitro data is strongly backed up by the results of the in vivo work which demonstrates matriptase-1 deficient cells have a substantially reduced ability to grow and develop in vivo compared to control cells when explanted into nude mice, with significant differences in growth and development (P &Mac178; 0.05) being seen after 7 days, and highly significant differences (p &Mac178; 0.001) after 15 days. Conclusions: Together this data strongly implicates matriptase-1 as playing a vital role in the aggressive nature and progression of prostate cancer.