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TIMP‐3 promotes apoptosis in nonadherent small cell lung carcinoma cells lacking functional death receptor pathway
Author(s) -
Kallio Janne P.,
HopkinsDonaldson Sally,
Baker Andrew H.,
Kähäri VeliMatti
Publication year - 2010
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/ijc.25404
Subject(s) - apoptosis , programmed cell death , cancer research , biology , receptor , caspase , extracellular matrix , caspase 8 , cell culture , microbiology and biotechnology , cell , signal transduction , biochemistry , genetics
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.