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Human Neuroendocrine Tumor Cell Lines as a Three-Dimensional Model for the Study of Human Neuroendocrine Tumor Therapy
Published on: August 14, 2012
Detection of functional interferon alpha receptors in human neuroendocrine tumor cell lines using a new monoclonal
A Rosolen1, O R Colamonici, L M Pfeffer
1Tumor Cell Biology Section, NCI, NIH, Bethesda, MD.
Abstract:
While first described as antiviral agents, interferons (IFNs) exhibit significant antiproliferative and antitumor effects as well. IFN alpha has been successfully used in clinical trials to treat several malignancies, including leukemias and certain solid tumors. While many cell types have been studied for IFN alpha receptor expression, very little is known about receptor expression on human neuroendocrine cells. Using a novel anti-IFN alpha receptor monoclonal antibody, we examined IFN alpha receptor expression in 10 human cell lines derived from tumors of neuroendocrine origin, including neuroblastoma, neuroepithelioma and small cell lung carcinoma. All cell lines studied displayed a similar pattern of IFN alpha receptor expression and 5 of 8 cell lines demonstrated reduced thymidine incorporation following IFN alpha treatment. Addition of exogenous IFN alpha caused a decrease in IFN alpha receptor expression, while differentiating agents, such as phorbol esters and retinoic acid, induced an increase in receptor number without altering receptor affinity.
Insights
Interferons (IFNs) show antitumor effects. This study investigated interferon alpha receptor expression on human neuroendocrine tumor cells, finding it present and influencing cell proliferation.
Area of Science:
- Immunology
- Oncology
- Molecular Biology
Background:
- Interferons (IFNs) possess known antiproliferative and antitumor properties.
- Interferon alpha (IFN-α) is clinically used against various malignancies.
- Receptor expression for IFN-α is well-characterized in many cell types, but not human neuroendocrine cells.
Purpose of the Study:
- To investigate Interferon alpha receptor (IFNAR) expression in human neuroendocrine tumor cell lines.
- To assess the functional impact of IFN-α on these cells.
- To explore the regulation of IFNAR expression by IFN-α and differentiating agents.
Main Methods:
- Utilized a novel anti-IFNAR monoclonal antibody for expression analysis.
- Examined 10 human neuroendocrine tumor cell lines (neuroblastoma, neuroepithelioma, small cell lung carcinoma).
- Assessed thymidine incorporation to measure antiproliferative effects of IFN-α.
- Investigated IFNAR expression changes upon treatment with IFN-α and differentiating agents (phorbol esters, retinoic acid).
Main Results:
- All tested neuroendocrine cell lines exhibited similar IFNAR expression patterns.
- IFN-α treatment reduced thymidine incorporation in 5 out of 8 evaluated cell lines.
- Exogenous IFN-α decreased IFNAR expression.
- Differentiating agents increased IFNAR number without affecting affinity.
Conclusions:
- Human neuroendocrine tumor cells express IFNAR.
- IFN-α can exert antiproliferative effects on a subset of these cells.
- IFNAR expression is dynamically regulated by IFN-α and differentiating agents, suggesting potential therapeutic modulation.
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