The cellular function and the role of
matriptase-2 in
cancer progression are poorly understood. This study assesses the importance of this
protease in
prostate cancer cell lines. Two
prostate cancer cell lines, PC-3 and DU-145, previously displaying minimal expression of
matriptase-2, were forced to over-express
matriptase-2 using a human mammalian expression construct. Over-expression of
matriptase-2 significantly reduced the invasive capacity and significantly slowed the migration rates of PC-3 and DU-145 cells in vitro. Similarly, PC-3 cells containing the
matriptase-2 expression plasmid were dramatically less able to survive, grow and develop into noticeable tumours, compared to control PC-3 cells containing an empty plasmid alone, following subcutaneous inoculation into CD1 nude mice. This trend was observed throughout the experiment, becoming apparent after the initial reading on day 7 (P = 0.0002) and continuing to the experimental end point at day 27 (P = 0.0002). Enhanced
matriptase-2 levels were also seen to correlate with increased fluorescent staining of the
paxillin and FAK adhesion molecules, where a greater extent of these molecules were localised to the focal adhesion complexes. This data suggests a suppressive role for
matriptase-2 in the invasion and migration of
prostate cancer cells in vitro and also in their development and growth in vivo, highlighting the potential of this molecule to interfere with key stages of
metastasis. Furthermore, the data presented implies a possible connection between
matriptase-2 and the
paxillin and FAK adhesion molecules which may ultimately contribute to the reduced migration rates seen in this study.