Natriuretic Peptide Receptor A as a Novel Anticancer Target

Abstract

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]

Vasoactive Peptides with Angiogenesis-Regulating Activity Predict Cancer Risk in Males

“…Several studies have documented an antiproliferative effect of ANP in endothelial cells as well as in different types of cancer cells (15)(16)(17)(18)(19)(20)(21). Indeed, it has been proposed that ANP counteracts tumorigenesis through feedback inhibition of its receptor, natriuretic peptide receptor A, that seems to drive tumor angiogenesis through VEGF induction (49). Moreover, endothelin-1-and VEGFdependent angiogenesis were inhibited by ANP (15,18,19), suggesting that ANP has opposing effects on some of the angiogenic signaling pathways triggered by ADM and vasopressin.…”

Ovarian stem cells: From basic to clinical applications

“…Side population Szotek et al [9] CD44/CD117 Zhang et al [10] Natriureticpeptide receptor A Kong et al [11] CD133 Ferradina et al [45] CD24 Gao et al [13] DEAD box polypeptide 4 Hashimoto et al [12] expressed DDX4 whereas the CD133-negative cells did not. The genetic program regulating the self-renewal and differentiation of CSCs plays a key role in cancer initiation, invasion and migration.…”

“…In 2004, Johnson et al [1] demonstrated the existence of proliferative GSCs in the ovaries of adult mice, and recently, ovarian GSCs have been isolated and characterized in the ovaries of postnatal mice and reproductive-age women [7] . Amid the controversy created by Johnson et al [1] , the presence of cancer stem cells (CSC) in ovarian cancer was established by Bapat et al [8] , and accumulating data have provided substantial evidence for the involvement of CSCs in ovarian cancer [9][10][11][12][13] . Ovarian cancer (OC) is associated with enhanced tumor aggressiveness and metastasis, as well as drug resistance.…”

BNP is a Novel Regulator of Embryonic Stem Cell Proliferation

“…BNP-transgenic mice exhibit overgrowth of the growth-plate cartilage through a cGMPdependent mechanism . Furthermore, signaling through NPR-A plays a pivotal role in tumor growth (Kong et al, 2008). Although little is known about the role of NPs in pre-implantation embryo development, one study reported that NPR-B-deficient mice were sterile due to a lack of development of the reproductive system, and the majority (75%) of the NPR-B-deficient mice studied died before 100 days of age (Tamura et al, 2004).…”