Secretion of atrial natriuretic peptide and vasopressin by small cell lung cancer

Abstract

Background. Hyponatremia in patients with small cell lung cancer (SCLC) is a common clinical problem usually attributed to tumor secretion of arginine vasopressin (AVP). It recently was shown that some SCLC cell lines produce atrial natriuretic peptide (ANP). The purpose of this investigation was to determine the frequency and clinical consequences of secretion of ANP by SCLC and the relative contribution of ANP and AVP to the hyponatremia associated with this disease. Methods. Levels of ANP and AVP were measured in 23 SCLC cell lines and 23 other human tumor cell lines. Also, ANP and AVP levels were determined in plasma samples from 69 patients with active small cell carcinomas. Results. Of the 23 SCLC lines, 16 (70%) had elevated ANP levels. Only two (8.7%) had elevated AVP levels, and these two also had elevated ANP levels. One of the ANP‐producing cell lines was derived from a hyponatremic patient with no other apparent explanation for a low sodium level. However, the four cell lines with the highest levels of ANP were derived from patients who were not hyponatremic. Two other human tumor lines also produced ANP. Of the 69 patients with SCLC, 21 (30.4%) had elevated ANP levels, whereas 4 (6%) had elevated AVP levels. Fifteen of these patients were hyponatremic during their clinical course (21.7%). Of the eight patients who were hyponatremic when samples were collected, two had e vated ANP levels, and only one had elevated AVP levels Six patients (8.7%) had symptoms of postural hypotension, possibly attributable in some cases to tumor secretion of ANP. Conclusions. The majority of SCLC lines produce ANP, and a minority produce AVP. Secretion of ANP may result in hyponatremia and/or postural hypotension. However, secretion of either or both of these peptic does not account for all cases of hyponatremia in patient with SCLC and does not necessarily cause clinical manifestations.

Novel cell lines for the analysis of preprotachykinin A gene expression identify a repressor domain 3′ of the major transcriptional start site

“…The NF2C cell line in particular might be a useful model delineating regulatory mechanisms that modulate rPPT promoter activity in neurons. The RIN cell lines might represent the dysregulation of rPPT promoter activity seen in tumours that exhibit a neuroendocrine phenotype [23][24][25][26] or they might reflect some developmental regulatory mechanisms operating on the rPPT promoter [21]. It is likely that the NF2C cells will be of more general use for analysis of neuronal gene expression because they have been reported to up-regulate the expression of neuronal markers on differentiation at 39 mC.…”

A Metabolic Study of Patients with Lung Cancer and Hyponatremia of Malignancy

“…Despite previous reports which have shown the ectopic tumor production of ANP mRNA (14,15), ANP immunoreactivity in tumor cells and supernatant (16,17), and reports of resolution of hyponatremia following surgical resection of ANP expressing tumors (16), no consistent prospective associations between elevated plasma ANP and hyponatremia have been reported in patients with lung cancer (4,15,16). Two studies of ANP in plasma and tumor cell lines showed no relationship between high levels of ANP and hyponatremia in patients with lung cancer (15,16).…”

“…Two studies of ANP in plasma and tumor cell lines showed no relationship between high levels of ANP and hyponatremia in patients with lung cancer (15,16). This has been explained, in part, by the potential effect which sodium intake has on ANP levels, causing wide variations in previously studied patients (22,23).…”

“…Ectopic production of ANP mRNA in tumors and tumor cell lines from patients with SCLC and hyponatremia has been documented by Northern blot, S 1 -nuclease analysis, RNase protection assay, and PCR (4,14,15). ANP has been detected in SCLC tumors and tumor cell lines by RIA (14,16,17). Characterization of the peptide from SCLC tumors and tumor cell lines by high-performance liquid chromatography has shown the peptide to be similar to the bioactive 28-amino acid form present in the plasma (17,18).…”

Neuropeptides and peptide hormones in syncope and orthostatic intolerance

“…Extrinsic pharmacologic agents (e.g., diuretics and vasodilators) are well-known causes of OH as noted above; however the possibility exists that intrinsic neurohumoral agents with similar properties may be a contributing factor was initially suggested by observations in certain paraneoplastic syndromes; specifically, findings in small cell lung cancer in which elevated ANP was associated with OH [24].…”