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Nerve growth factor abrogates the tumorigenicity of human small cell lung cancer cell lines
C Missale1, A Codignola, S Sigala
1Department of Biomedical Sciences and Biotechnology, Division of Pharmacology, University of Brescia, Via Valsabbina 19, 25124, Brescia, Italy. cmissale@med.unibs.it
Abstract:
Nerve growth factor (NGF) has antiproliferative and differentiating effects on adenomas of neuroendocrine origin. Cell lines derived from small-cell lung carcinoma (SCLC), a very aggressive neuroendocrine tumor, express NGF receptors. The role of NGF in the control of proliferation and progression of this carcinoma, however, has never been investigated. Chronic exposure of NCI-N-592 and GLC8 SCLC cell lines to NGF remarkably inhibited their proliferation rate both in vitro and in vivo, prevented their anchorage-independent clonal growth in soft agar, impaired their invasive capacity in vitro, and abolished their tumorigenic potential in nude mice. The proliferative response of SCLC cell lines to nicotine was also remarkably impaired by in vitro NGF treatment. Furthermore, NGF treatment activates in SCLC cell lines the expression and secretion of NGF. NGF thus reverts SCLC cell lines to a noninvasive, nontumorigenic phenotype that does not respond to nicotine and produces NGF.
Insights
Nerve growth factor (NGF) inhibits small-cell lung carcinoma (SCLC) cell growth and invasiveness. NGF treatment also reduces SCLC
Area of Science:
- Oncology
- Neuroscience
- Cell Biology
Background:
- Neuroendocrine tumors, including small-cell lung carcinoma (SCLC), are aggressive cancers.
- Nerve growth factor (NGF) exhibits antiproliferative effects on neuroendocrine adenomas.
- NGF receptors are expressed in SCLC cell lines, suggesting a potential role for NGF.
Purpose of the Study:
- To investigate the role of NGF in controlling the proliferation and progression of SCLC.
- To determine if NGF can reverse the aggressive phenotype of SCLC cells.
Main Methods:
- Chronic exposure of NCI-N-592 and GLC8 SCLC cell lines to NGF.
- In vitro assays for proliferation, anchorage-independent growth, and invasion.
- In vivo tumorigenicity studies in nude mice.
- Assessment of SCLC cell response to nicotine after NGF treatment.
Main Results:
- NGF significantly inhibited SCLC cell proliferation in vitro and in vivo.
- NGF prevented anchorage-independent growth and reduced invasive capacity.
- NGF abolished the tumorigenic potential of SCLC cells in nude mice.
- NGF treatment impaired the proliferative response of SCLC cells to nicotine.
- NGF induced NGF expression and secretion in SCLC cell lines.
Conclusions:
- NGF reverts SCLC cells to a noninvasive, nontumorigenic phenotype.
- NGF-treated SCLC cells exhibit reduced responsiveness to nicotine.
- NGF promotes a self-sustaining inhibitory loop by inducing its own production in SCLC cells.