Tumor necrosis factor induces neuroendocrine differentiation in small cell lung cancer cell lines.

Journal Article (Journal Article)

We studied tumor necrosis factor (TNF)-alpha as a candidate cytokine to promote neuroendocrine cell differentiation in a nitrosamine-hyperoxia hamster lung injury model. Differential screening identified expression of the genes modulated by TNF-alpha preceding neuroendocrine cell differentiation. Undifferentiated small cell lung carcinoma (SCLC) cell lines NCI-H82 and NCI-H526 were treated with TNF-alpha for up to 2 wk. Both cell lines demonstrated rapid induction of gastrin-releasing peptide (GRP) mRNA; H82 cells also expressed aromatic-L-amino acid decarboxylase mRNA within 5 min after TNF-alpha was added. Nuclear translocation of nuclear factor-kappaB immunostaining occurred with TNF-alpha treatment, suggesting nuclear factor-kappaB involvement in the induction of GRP and/or aromatic-L-amino acid decarboxylase gene expression. We also demonstrated dense core neurosecretory granules and immunostaining for proGRP and neural cell adhesion molecule in H82 cells after 7-14 days of TNF-alpha treatment. We conclude that TNF-alpha can induce phenotypic features of neuroendocrine cell differentiation in SCLC cell lines. Similar effects of TNF-alpha in vivo may contribute to the neuroendocrine cell differentiation/hyperplasia associated with many chronic inflammatory pulmonary diseases.

Full Text

Duke Authors

Cited Authors

  • Haley, KJ; Patidar, K; Zhang, F; Emanuel, RL; Sunday, ME

Published Date

  • August 1998

Published In

Volume / Issue

  • 275 / 2

Start / End Page

  • L311 - L321

PubMed ID

  • 9700092

International Standard Serial Number (ISSN)

  • 0002-9513

Digital Object Identifier (DOI)

  • 10.1152/ajplung.1998.275.2.L311


  • eng

Conference Location

  • United States