Galanin and galanin receptors in human cancers

Berger, Alexandra; Santic, Radmila; Hauser‐Kronberger, Cornelia; Schilling, Freimut H.; Kogner, Per; Ratschek, Manfred; Gamper, Agnes; Jones, Neil D.; Sperl, Wolfgang; Kofler, Barbara

doi:10.1016/j.npep.2004.12.016

Cited by 51 publications

(40 citation statements)

References 60 publications

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“…Consistent with the wide distribution galanin has been shown to have broad range of neuroendocrine and physiological actions. Furthermore, neuropeptides, again including galanin, are known to be expressed in tumors of the CNS and especially neuroendocrine tumors in the periphery (46). Given that alarin might be another member of the increasing family of neuropeptides it is not surprising that its expression has been reported recently in ganglionic cells of human neuroblastic tumors (18), and now we show a vascular function.…”

Section: Discussionsupporting

confidence: 56%

Alarin is a vasoactive peptide

Santic¹,

Schmidhuber²,

Lang

et al. 2007

Proc. Natl. Acad. Sci. U.S.A.

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Galanin-like peptide (GALP) is a hypothalamic neuropeptide belonging to the galanin family of peptides. The GALP gene is characterized by extensive differential splicing in a variety of murine tissues. One splice variant excludes exon 3 and results in a frame shift leading to a novel peptide sequence and a stop codon after 49 aa. In this peptide, which we termed alarin, the signal sequence of the GALP precursor peptide and the first 5 aa of the mature GALP are followed by 20 aa without homology to any other murine protein. Alarin mRNA was detected in murine brain, thymus, and skin. In accordance with its vascular localization, the peptide exhibited potent and dose-dependent vasoconstrictor and anti-edema activity in the cutaneous microvasculature, as was also observed with other members of the galanin peptide family. However, in contrast to galanin peptides in general, the physiological effects of alarin do not appear to be mediated via the known galanin receptors. Alarin adds another facet to the surprisingly high-functional redundancy of the galanin family of peptides.galanin-like peptide ͉ regulatory peptide ͉ splicing ͉ plasma extravasation ͉ cutaneous microvasculature

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Section: Discussionsupporting

confidence: 56%

Alarin is a vasoactive peptide

Santic¹,

Schmidhuber²,

Lang

et al. 2007

Proc. Natl. Acad. Sci. U.S.A.

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“…Three galanin receptors (GAL-R1, GAL-R2, and GAL-R3) have been clone thus far. These receptors belong to the family of G protein -coupled receptor superfamily (2). Galanin was coexpressed with its receptors whatever the differentiation stage in neuroblastic tumors (8).…”

Section: Discussionmentioning

confidence: 99%

“…Colorectal cancer is the most common gastrointestinal cancer in the Western world and it is an important cause of cancer-related death (1,2). An overall 5-year survival rate is f50%.…”

Section: Introductionmentioning

confidence: 99%

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Galanin Is Up-Regulated in Colon Adenocarcinoma

Kim¹,

Kee²,

Chong

et al. 2007

Cancer Epidemiology, Biomarkers &Amp; Prevention

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The early diagnosis of colorectal cancer and the early detection of recurrence are central to effective treatment, as prognosis is directly related to the stage of the disease. When colorectal cancer is diagnosed at an early, localized stage, 5-year survival is 90%. There is substantial interest in the identification of circulating human tumor-derived proteins in serum for the purposes of early cancer diagnosis. We have implemented an approach based on the analysis of microarray data for the identification of tumor proteins that may have utility as biomarkers in colon cancer. Expression analysis of microarray data obtained from a variety of 290 tumors and normal tissues revealed that galanin was maximally expressed in colon cancer. These findings were corroborated by real-time quantitative PCR, in which the colon cancer cell lines LOVO, HCT15, SW480, and SW620 cell showed significantly higher levels of galanin expression than did noncolon cancer cell lines. To evaluate galanin as a potential biomarker of colon cancer, a preliminary ''training'' set of serum from 40 healthy donors and 55 colon cancer patients was analyzed by ELISA. The data pattern was confirmed by an independent set of 90 masked serum samples: 24 from healthy donors and 66 from colon cancer patients. This result yielded a sensitivity of 69.7% [95% confidence interval (95% CI), 57.1-80.4], specificity of 75.0% (95% CI, 53.3-90.2), and positive predictive value of 88.5% (95% CI, 76.6-95.7). The galanin expression level was significantly increased with tumor size and tumor stage. These findings justify a prospective assessment of serum galanin protein as a screening tool for colon cancer. (Cancer Epidemiol Biomarkers Prev 2007;16(11):2373 -8)

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“…GALP is localized in the brain and its gene has been partially characterized in mice, rats, macaques and humans [32][33][34][35][36]. Cells in the Arc and median eminence of the rat, mouse and monkey express GALP mRNA [35,37].…”

Section: Expression Of Galp In the Brainmentioning

confidence: 99%

Galanin-like peptide as a link in the integration of metabolism and reproduction

Gottsch

Clifton

Steiner

2004

Trends in Endocrinology & Metabolism

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The arcuate nucleus is a hypothalamic center that couples energetics and reproduction. Peptide-releasing neurons in the arcuate nucleus receive and process humoral signals from the periphery and relay this information to other nuclei in the hypothalamus and preoptic area. Galanin-like peptide (GALP) is expressed in the arcuate nucleus, and GALP-containing neurons are targets for the action of leptin. GALP-containing neurons are closely apposed to gonadotropin-releasing hormone (GnRH) neurons in the preoptic area, and CNS injections of GALP stimulate GnRH-mediated secretion of luteinizing hormone. These observations indicate that GALP is a molecular signal that couples circulating indices of metabolism to the neuroendocrine reproductive system and, thus, regulates reproductive activity as a function of the energy state. In this article, we describe the involvement of GALP in metabolism and reproduction, and in the coupling between these two processes.The brain has a remarkable ability to sense the status of metabolic fuel reserves and defend their adequacy by adjusting appetite and metabolism to maintain an appropriate body weight. Moreover, the brain governs the activity of the reproductive system as a function of these metabolic reserves and enables activation of the hypothalamic -pituitary -gonadal axis only when fuel stores are deemed adequate to support the energetic requirements of reproduction. The arcuate nucleus (Arc) in the hypothalamus is a node for this physiological integration. Recently, a newly identified peptide in the Arc has been shown to modulate both feeding behavior and reproduction, which unveils a new link in the integration of metabolism and reproduction. In this review, we discuss the emerging role of this peptide, known as galanin-like peptide (GALP), in the physiological integration of metabolism and reproduction. The Arc integrates metabolism and reproductionThe Arc comprises the neuronal circuitry required for the neuroendocrine integration of metabolism and reproduction [1]. Two populations of neurons in the Arc play key roles in the regulation of these physiological processes. One population produces neuropeptide Y (NPY) and agouti-related peptide (AgRP), whereas the other produces a-melanocyte-stimulating hormone (a-MSH) and b-endorphin from a common precursor, proopiomelanocortin (POMC), and cocaine-and amphetamine-regulated transcript (CART). These two cell groups (NPY/AgRP and POMC/CART) are regulated differentially by metabolic hormones such as leptin and insulin, and act in opposition to control appetite, body weight and metabolic rate [1][2][3][4]. NPY/AgRP and POMC/CART neurons send axonal projections to the paraventricular nucleus (PVN), lateral hypothalamus, and areas in the midbrain and hindbrain to regulate the circuitry that controls complex behaviors, such as feeding, and adjust the metabolic rate to maintain body weight homeostasis [3,[5][6][7]. Disruption of these networks leads to the dysregulation of body weight and disturbances in metabolism [8]. The Arc is also a...

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Galanin and galanin receptors in human cancers

Cited by 51 publications

References 60 publications

Alarin is a vasoactive peptide

Alarin is a vasoactive peptide

Galanin Is Up-Regulated in Colon Adenocarcinoma

Galanin-like peptide as a link in the integration of metabolism and reproduction

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