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ANP secretion from small cell lung cancer cell lines: a potential model of ANP release
D A Wigle1, B G Campling, I R Sarda
1Department of Anatomy and Cell Biology, Queen's University, Kingston, Ontario, Canada.
Abstract:
Although atrial distension is widely accepted as the primary stimulus for atrial natriuretic peptide (ANP) release, a number of agonists are also known to induce its secretion. The mechanisms underlying these processes are not well understood. Studies of this nature are hampered by the inherent difficulty in culturing homogeneous populations of cardiac myocytes in sufficient quantities to perform molecular investigations. For this reason, we have examined the possibility of using other cell types as a model of ANP release. It has been reported that a number of tumor samples from small cell lung cancer (SCLC) patients express the ANP gene. Characterization of a large number of cell lines derived from SCLC tumor samples indicated that two of these cell lines, OS-A and SHP-77, secrete ANP at rates of approximately 10(-20) g.cell-1.min-1. This is a sufficient quantity to facilitate secretion studies using a perifusion system. We have demonstrated that ANP is released through regulated secretory pathways, as the Ca2+ ionophore A-23187, arginine vasopressin (AVP), and the sodium ionophore, monensin, were capable of modifying secretion rates. High-pressure liquid chromatography (HPLC) analysis indicated that the primary secretory product is ANP-(99-126), the circulating form of this hormone. Intracellularly, both ANP-(99-126) and ANP-(1-126) were present, suggesting the synthesis and appropriate cleavage of pro-ANP-(1-126). Because both of these cell lines have doubling times in the range of 3-5 days, they could serve as a rapidly proliferating and easily maintainable supply of homogeneous tissue for release studies.(ABSTRACT TRUNCATED AT 250 WORDS)
Insights
Small cell lung cancer cell lines secrete atrial natriuretic peptide (ANP), offering a novel model for studying ANP release mechanisms. These cells provide a homogeneous and rapidly proliferating source for secretion studies.
Area of Science:
- Endocrinology
- Cell Biology
- Molecular Biology
Background:
- Atrial natriuretic peptide (ANP) release is primarily stimulated by atrial distension, but other agonists also induce secretion.
- Mechanisms of ANP secretion are not fully understood, partly due to difficulties in culturing cardiac myocytes.
- Small cell lung cancer (SCLC) tumors have been reported to express the ANP gene.
Purpose of the Study:
- To investigate the use of SCLC cell lines as a model for studying ANP release.
- To characterize ANP secretion from SCLC cell lines OS-A and SHP-77.
- To determine the pathways involved in ANP release from these cell lines.
Main Methods:
- Cultured and characterized SCLC cell lines (OS-A, SHP-77) for ANP secretion.
- Utilized a perifusion system to study ANP release rates.
- Employed HPLC to analyze the secreted ANP products.
- Investigated the effect of agonists like A-23187, AVP, and monensin on secretion.
Main Results:
- Two SCLC cell lines, OS-A and SHP-77, secrete significant quantities of ANP.
- ANP release occurs via regulated secretory pathways, modulated by ionophores and AVP.
- HPLC analysis confirmed the primary secreted product as ANP-(99-126), the active hormone.
- Intracellularly, both pro-ANP and cleaved forms were detected, indicating proper synthesis and processing.
Conclusions:
- SCLC cell lines provide a viable and practical model for studying ANP secretion.
- These cell lines facilitate molecular investigations into ANP release mechanisms.
- The characterized cell lines offer a homogeneous and rapidly proliferating source for research.
