TIMP-3 promotes apoptosis in nonadherent small cell lung carcinoma cells lacking functional death receptor pathway

Janne P Kallio, Sally Hopkins-Donaldson, Andrew H Baker, Veli-Matti Kähäri

Research output: Contribution to journalArticlepeer-review

Abstract

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.

Original languageEnglish
Pages (from-to)991-6
Number of pages6
JournalInternational Journal of Cancer
Volume128
Issue number4
DOIs
Publication statusPublished - 15 Feb 2011

Keywords

  • Adenoviridae
  • Apoptosis
  • Caspase 3
  • Caspase 8
  • Humans
  • Lung Neoplasms
  • Melanoma
  • Receptors, Death Domain
  • Small Cell Lung Carcinoma
  • Tissue Inhibitor of Metalloproteinase-3
  • Tumor Cells, Cultured

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