TIMP-3 promotes apoptosis in nonadherent small cell lung carcinoma cells lacking functional death receptor pathway.
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.
Kallio
Janne P
JP
Department of Dermatology, University of Turku and Turku University Hospital and MediCity Research Laboratory, University of Turku, Turku, Finland.
Hopkins-Donaldson
Sally
S
Baker
Andrew H
AH
Kähäri
Veli-Matti
VM
D000256:Adenoviridae / Q000235:genetics; D017209:Apoptosis; D053148:Caspase 3 / Q000378:metabolism; D053181:Caspase 8 / Q000378:metabolism; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D008545:Melanoma / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D053218:Receptors, Death Domain / Q000172:deficiency*; D055752:Small Cell Lung Carcinoma / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D019717:Tissue Inhibitor of Metalloproteinase-3 / Q000235:genetics / Q000378:metabolism*; D014407:Tumor Cells, Cultured
D053218:Receptors, Death Domain; C088390:TIMP3 protein, human; D019717:Tissue Inhibitor of Metalloproteinase-3; D053148:Caspase 3; D053181:Caspase 8