Expression of the Atrial Natriuretic Factor Gene in small Cell Lung Cancer Tumors and Tumor Cell Lines

Bliss, David P.; Battey, James F.; Linnoila, R. Ilona; Birrer, Michael J.; Gazdar, Adi F.; Johnson, Bruce E.

doi:10.1093/jnci/82.4.305

Cited by 51 publications

(24 citation statements)

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“…Increased IL-6 in lung cancer patients enhances the acute phase response and is correlated with poor nutritional status and lowered survival (13). Both ANP and NPRA are expressed by lung cancer cells, and oversecretion of ANP has been linked with hyponatremia (14)(15)(16). However, little is known about the effects of NPRA signaling on inflammation and cancer progression.…”

Section: Introductionmentioning

confidence: 99%

Natriuretic Peptide Receptor A as a Novel Anticancer Target

Kong¹,

Wang

et al. 2008

Cancer Research

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The receptor for atrial natriuretic peptide (ANP), natriuretic peptide receptor A (NPRA), is expressed in cancer cells, and natriuretic peptides have been implicated in cancers. However, the direct role of NPRA signaling in tumorigenesis remains elusive. Here, we report that NPRA expression and signaling is important for tumor growth. NPRA-deficient mice showed significantly reduced antigen-induced pulmonary inflammation. NPRA deficiency also substantially protected C57BL/6 mice from lung, skin, and ovarian cancers. Furthermore, a nanoparticle-formulated interfering RNA for NPRA attenuated B16 melanoma tumors in mice. Ectopic expression of a plasmid encoding NP73-102, the NH 2 -terminal peptide of the ANP prohormone, which down-regulates NPRA expression, also suppressed lung metastasis of A549 cells in nude mice and tumorigenesis of Line 1 cells in immunocompetent BALB/c mice. The antitumor activity of NP73-102 was in part attributed to apoptosis of tumor cells. Western blot and immunohistochemistry staining indicated that the transcription factor, nuclear factor-KB, was inactivated, whereas the level of tumor suppressor retinoblastoma protein was upregulated in the lungs of NPRA-deficient mice. Furthermore, expression of vascular endothelial growth factor was downregulated in the lungs of NPRA-deficient mice compared with that in wild-type mice. These results suggest that NPRA is involved in tumor angiogenesis and represents a new target for cancer therapy. [Cancer Res 2008;68(1):249-56]

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Section: Introductionmentioning

confidence: 99%

Natriuretic Peptide Receptor A as a Novel Anticancer Target

Kong¹,

Wang

et al. 2008

Cancer Research

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“…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).…”

Section: Discussionmentioning

confidence: 78%

“…However, SCLC patients with hyponatremia have been described who have no measurable AVP in their tumors (12), tumor cell lines (13), or in their plasma (10,14). 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).…”

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confidence: 99%

“…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).…”

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confidence: 99%

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

Chute

Taylor

et al. 2006

Clinical Cancer Research

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Purpose: One-third of patients with lung cancer and hyponatremia have no evidence of ectopic arginine vasopressin (AVP) production and the cause of their hyponatremia is not conclusively established.We sought to distinguish patients with hyponatremia caused by elevated AVP versus those with ectopic atrial natriuretic peptide (ANP) via this detailed metabolic study. Experimental Design: We enrolled 24 patients recently diagnosed with lung cancer in a metabolic study in which patients were placed on sodium and fluid restriction for 4 days. Serum electrolytes, osmolality, urine electrolytes and osmolality, plasma AVP, ANP, aldosterone, urinary cyclic AMP and cyclic guanosine 3V,5V-monophosphate were measured daily and tumor tissue was obtained to measure ectopic hormone production.We attempted to characterize the pathophysiology of hyponatremia caused by ectopic ANP production in patients with small cell lung cancer (SCLC) and to determine its effect on the aldosterone axis. Results: Seven of the nine patients with SCLC presented with hyponatremia and three had elevated ANP levels at presentation without elevation of AVP. All three patients who presented with hyponatremia and elevated ANP showed a decline in serum sodium following fluid restriction, whereas two patients with SCLC and elevated AVP had normalized serum sodium levels. The combination of hyponatremia and elevated ANP was associated with a persistent natriuresis and inappropriately low aldosterone levels despite sodium restriction, suggesting ANP suppression of the aldosterone axis. Conclusions: Management of patients with hyponatremia and SCLC should be guided by the knowledge that some patients with SCLC have ectopic production of ANP as the cause of their hyponatremia.

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“…Paraneoplastic hyponatremia secondary to elevated atrial natriuretic peptide (ANP) has also been reported [31] . Most SCLC cell lines have been shown to produce ANP [32,33] . Of the 23 SCLC lines examined, 16 (70%) had elevated ANP levels [33] , whereas only two (8.7%) had elevated ADH levels, and these two also had elevated ANP levels [33] .…”

Section: Hhmmentioning

confidence: 99%

Paraneoplastic syndromes associated with lung cancer

1993

Lung Cancer

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Paraneoplastic syndromes are signs or symptoms that occur as a result of organ or tissue damage at locations remote from the site of the primary tumor or metastases. Paraneoplastic syndromes associated with lung cancer can impair various organ functions and include neurologic, endocrine, dermatologic, rheumatologic, hematologic, and ophthalmological syndromes, as well as glomerulopathy and coagulopathy (Trousseau's syndrome). The histological type of lung cancer is generally dependent on the associated syndrome, the two most common of which are humoral hypercalcemia of malignancy in squamous cell carcinoma and the syndrome of inappropriate antidiuretic hormone secretion in small cell lung cancer. The symptoms often precede the diagnosis of the associated lung cancer, especially when the symptoms are neurologic or dermatologic. The proposed mechanisms of paraneoplastic processes include the aberrant release of humoral mediators, such as hormones and hormone-like peptides, cytokines, and antibodies. Treating the underlying cancer is generally the most effective therapy for paraneoplastic syndromes, and treatment soon after symptom onset appears to offer the best potential for symptom improvement. In this article, we review the diagnosis, potential mechanisms, and treatments of a wide variety of paraneoplastic syndromes associated with lung cancer.

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Expression of the Atrial Natriuretic Factor Gene in small Cell Lung Cancer Tumors and Tumor Cell Lines

Cited by 51 publications

References 0 publications

Natriuretic Peptide Receptor A as a Novel Anticancer Target

Natriuretic Peptide Receptor A as a Novel Anticancer Target

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

Paraneoplastic syndromes associated with lung cancer

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