Inhibition of ADAM9 expression induces epithelial phenotypic alterations and sensitizes human prostate cancer cells to radiation and chemotherapy

INTRODUCTION Recent studies demonstrated the importance of ADAM9 in prostate cancer relapse upon therapy. In this study, we determined the role of ADAM9 in the therapeutic resistance to radiation and chemotherapy. MATERIALS AND METHODS ADAM9 was either transiently or stably knocked down in C4-2 prostate cancer cells. The sensitivity of ADAM9 knockdown cells toward radiation and chemotherapeutic agents were determined. Additionally, the effects of ADAM9 knockdown on prostate cancer cell morphology, biochemical and functional alterations were accessed. RESULTS Both transient and stable knockdown of ADAM9 resulted in increased apoptosis and increased sensitivity to radiation. ADAM9 knockdown also increased prostate cancer sensitivity to several chemotherapeutic drugs. ADAM9 knockdown resulted in increased E-cadherin and altered integrin expression and underwent phenotypic epithelial transition. These were reflected by the morphological, biochemical, and functional alterations in the ADAM9 knockdown cells. CONCLUSIONS ADAM9 plays a crucial role in prostate cancer progression and therapeutic resistance in part by altering E-cadherin and integrin expression. ADAM9 is an important target for the consideration of treating prostate cancer patients who developed therapeutic resistance and disease relapse. Prostate