Galanin and galanin receptor expression in neuroblastic tumours: correlation with their differentiation status

Abstract

Neuroblastoma and its benign differentiated counterpart, ganglioneuroma, are paediatric neuroblastic tumours arising in the sympathetic nervous system. Their broad spectrum of clinical virulence is mainly related to heterogeneous biologic background and tumour differentiation. Neuroblastic tumours synthesize various neuropeptides acting as neuromodulators. Previous studies suggested that galanin plays a role in sympathetic tissue where it could be involved in differentiation and development. We investigated the expression and distribution of galanin and its three known receptors (Gal-R1, Gal-R2, Gal-R3) in 19 samples of neuroblastic tumours tissue by immunohistochemistry, in situ hybridization and fluorescent-ligand binding. This study provides clear evidence for galanin and galanin receptor expression in human neuroblastic tumours. The messengers coding for galanin, Gal-R1 and -R3 were highly expressed in neuroblastoma and their amount dramatically decreased in ganglioneuroma. In contrast, Gal-R2 levels remained unchanged. Double labelling studies showed that galanin was mainly coexpressed with its receptors whatever the differentiation stage. In neuroblastic tumours, galanin might promote cell-survival or counteract neuronal differentiation through the different signalling pathways mediated by galanin receptors. Finally, our results suggest that galanin influences neuroblastoma growth and development as an autocrine/paracrine modulator. These findings suggest potential critical implications for galanin in neuroblastic tumours development.

Galanin Is Up-Regulated in Colon Adenocarcinoma

“…As galanin is an inhibitory factor in regulating cell proliferation (9-13), the protection mechanism would be increased with the cancer growth. Indeed, galanin expression was increased in testicular germ cell and neuroblastic cancers with a possible direct influence on cancer proliferation (8,14). Interestingly, cytolytic effects in tissues were occasionally correlated with the presence of galanin in the study.…”

“…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). The detection of galanin in the human colon cancer cells indicates that these epithelial cells play a key role in host defense of the bowel.…”

“…A few reports have indicated the presence of galanin in gliomas, pheochromocytomas, and pituitary and neuroblastic tumors (2,8). There is much interest in identification of circulating tumorderived proteins that may serve as a biomarker for the early detection of colon cancer.…”

Physiology, Signaling, and Pharmacology of Galanin Peptides and Receptors: Three Decades of Emerging Diversity

“…In 1994, GAL 1 was cloned from the human Bowes melanoma cell line (Habert-Ortoli et al, 1994) and is the most prominently expressed galanin receptor in human meningioma, glioblastoma (Berger et al, 2003) and neuroblastoma (Berger et al, 2002), and elevated GAL 1 expression is associated with increased malignancy (Perel et al, 2002). Increased GAL 1 expression was also observed in human pituitary adenomas relative to levels in normal human pituitaries (Tofighi et al, 2012), suggesting cancer-promoting properties for GAL 1 , at least in these tumors.…”

“…Indeed, a correlation between the amount of galanin in neuroblastoma and their differentiation status was reported (Perel et al, 2002), although a similar study could not confirm this correlation (Berger et al, 2002) Galanin was also detected in a variety of nonneuroendocrine human tumors of different origin, including glioblastoma and other brain tumors (Berger et al, 2003), melanoma (Gilaberte et al, 2007), head and neck squamous cell carcinoma (HNSCC) (Sugimoto et al, 2009), basal cell carcinoma (Kepron et al, 2009), colon cancer (Kim et al, 2007;Godlewski and Pidsudko, 2012;Stevenson et al, 2012), and embryonic carcinoma (Skotheim et al, 2005). Interestingly, the majority of these tumors exhibited significantly higher galanin levels than corresponding noncancerous tissue (Skotheim et al, 2005;Gilaberte et al, 2007;Kim et al, 2007;Sugimoto et al, 2009;Stevenson et al, 2012), similar to observations of human pheochromocytoma (Bauer et al, 1986c).…”