Tissue inhibitor of metalloproteinases-3 (TIMP-3) has previously been identified as a tumor suppressor for adherent malignant and normal cells. TIMP-3 inhibits adhesion of cells to extracellular matrix and promotes apoptosis through death receptor-activated, caspase-8-mediated pathway. Here, we have studied the effect of adenovirally mediated overexpression of TIMP-3 on small cell lung cancer (SCLC) cell lines SW2 and N417, which grow in suspension and lack functional caspase-8. The results show that adenoviral delivery of TIMP-3 promotes apoptotic cell death in SCLC cells in the absence of caspase-8 activation. These results suggest TIMP-3 as a promising therapeutic anticancer protein also in nonadherent malignant cells lacking functional death receptor signaling.
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