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

Abstract

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.

• Authors: K J Haley, K Patidar, F Zhang, R L Emanuel, M E Sunday
• Journal: The American journal of physiology (Am J Physiol) Vol. 275 Issue 2 Pg. L311-21 (08 1998) ISSN: 0002-9513 [Print] United States
• PMID: 9700092 (Publication Type: Journal Article, Research Support, U.S. Gov't, P.H.S.)

Chemical References

• Biomarkers
• NF-kappa B
• Nitrosamines
• RNA, Messenger
• Tumor Necrosis Factor-alpha
• Gastrin-Releasing Peptide
• Aromatic-L-Amino-Acid Decarboxylases

Topics

• Animals
• Aromatic-L-Amino-Acid Decarboxylases (biosynthesis, genetics)
• Biomarkers
• Carcinoma, Small Cell (pathology)
• Cell Differentiation
• Cricetinae
• Cytoplasmic Granules (metabolism, ultrastructure)
• Gastrin-Releasing Peptide (biosynthesis, genetics)
• Humans
• Hyperoxia
• Lung (cytology, drug effects, pathology)
• Lung Neoplasms (pathology)
• NF-kappa B (metabolism)
• Neurosecretory Systems (cytology, drug effects)
• Nitrosamines
• RNA, Messenger (biosynthesis)
• Transcription, Genetic (drug effects)
• Tumor Cells, Cultured
• Tumor Necrosis Factor-alpha (pharmacology)