Identifying the Key Molecular Drivers of Prostate Cancer Cell Migration and Metastasis

INTRODUCTION<br/>Prostate cancer is the second leading cause of male cancer-related deaths in Australia. This high mortality risk has been increasingly linked to metastatic disease status. However, the specific molecular factors that drive tumour cell migration, and thus the metastatic potential of prostate cancer cells, remain poorly understood. <br/><br/>METHODS<br/>Minimally (LNCaP) and highly (PC3) metastatic prostate cancer cell lines with varying levels of tumorigenicity and androgen sensitivity were assessed for cell motility markers. This was completed through differential gene expression analysis of n=84 cell motility genes in the highly vs. minimally metastatic models performed in triplicate. <br/><br/>RESULTS<br/>The genes with the highest fold-change expression (p&lt;0.001) in the highly metastatic prostate cancer model compared to the minimally metastatic model were CAV1, FGF2, ITGB2, MET, MMP14, PLD1, RAC2, RND3, TGFB1 and VIM. On the other hand, expression of IGF1, PTEN, and STAT3 was lost in the highly metastatic model compared to the minimally metastatic model. Interestingly, MMP14 or Matrix Metalloproteinase-14, a zinc-dependent protease that plays a major role in the remodelling and breakdown of the extracellular matrix, had a higher gene expression than other proteases (MMP2, MMP9) in both the highly and minimally metastatic models, suggesting it has a significant involvement in prostate cancer cell migration. <br/><br/>CONCLUSION<br/>Developing our understanding of cell motility gene expression in prostate cancer metastasis has the potential to contribute to our understanding of the mechanisms of prostate cancer progression, influencing the development of targets for treatment and markers for diagnosis and prognosis in prostate cancer.