Critical Role of ADAM15 in Tumor Progression: Targeting Multiple Factors for Metastasis Promotion

Abstract

Evaluation of: Najy AJ, Day KC, Day ML: ADAM15 supports prostate cancer metastasis by modulating tumor cell–endothelial cell interaction. Cancer Res. 68, 1092–1099 (2008). Products of a disintegrin and metalloproteinase (ADAM) gene family are multifunctional proteins and have activities of metalloproteinase, integrin-binding, cell adhesion and intracellular signaling. ADAMs play important roles in many biological processes, such as neurogenesis, myogenesis, fertilization and growth factor shedding. Several ADAM genes are also implicated in various types of cancers; however, the exact function of ADAMs in tumorigenesis and tumor progression has not been well understood. In this report, Najy and colleagues have shown that ADAM15 plays a critical role in tumor growth and metastasis in human prostate cancer. Their results indicate that ADAM15 promotes the binding to extracellular matrix proteins, expression of metastatic-associated cell surface proteins, cleavage of N-cadherin and activation of matrix metalloproteinase 9. These events were followed by stimulation of transendothelial migration and bone metastasis. Therefore, ADAM15 signaling may serve as a potential therapeutic target for prostate cancer.