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
Language
- eng
Conference Location
- United States