engleski

Nm23-H1 and Nm23-H2 cooperate to reduce prostate cancer cell migration

Nm23-H1 and Nm23-H2 are ubiquitously expressed proteins involved in maintaining nucleotide homeostasis as well as cell differentiation, development and metastatic dissemination. In the cell they form homohexameres and heterohexameres in all subunit combinations. Increased expression of either of these proteins decreases metastatic potential of most but not all tumor cells investigated as well as outgrowth of distant metastases. Although highly similar and part of the same multimeric complex, it seems that Nm23-H1 and Nm23-H2 also have distinctive functions in the cell. Thus we aimed to analyze the effect of both total amount of either of the proteins expressed and their relative expression on metastatic potential of tumor cells in vitro. Using adenoviral based vector system we varied expression of Nm23-H1 and/or Nm23-H2 in prostate cancer cell lines (PC3 and DU145) and correlated to their migratory ability. Our results show that using this approach we can establish the expression of both Nm23-H1 and Nm23-H2 in desired ratios in cell lines examined. Additionally, our preliminary results suggest that Nm23-H1 and Nm23-H2 act synergistically to inhibit migration at least in some of the highly metastatic prostate cancer cell lines. Determining ratios of Nm23- H1 and Nm23-H2 expression in tumor cells that have the highest potency for reducing metastatic potential and hopefully outgrowth of distant metastasis has potential application in cancer management as a prognostic marker or development of viral vector based therapy for metastatic disease.

Nm23; metastasis suppressor; adenoviral; prostate cancer; cell migration

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