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Galanin System in Human Glioma and Pituitary Adenoma. 2020

Sarah Falkenstetter, and Julia Leitner, and Susanne M Brunner, and Tim N Rieder, and Barbara Kofler, and Serge Weis
Research Program for Receptor Biochemistry and Tumor Metabolism, Department of Pediatrics, University Hospital of the Paracelsus Medical University, Salzburg, Austria.

Expression of neuropeptides and their corresponding receptors has been demonstrated in different cancer types, where they can play a role in tumor cell growth, invasion, and migration. Human galanin (GAL) is a 30-amino-acid regulatory neuropeptide which acts through three G protein-coupled receptors, GAL1-R, GAL2-R, and GAL3-R that differ in their signal transduction pathways. GAL and galanin receptors (GALRs) are expressed by different tumors, and direct involvement of GAL in tumorigenesis has been shown. Despite its strong expression in the central nervous system (CNS), the role of GAL in CNS tumors has not been extensively studied. To date, GAL peptide expression, GAL receptor binding and mRNA expression have been reported in glioma, meningioma, and pituitary adenoma. However, data on the cellular distribution of GALRs are sparse. The aim of the present study was to examine the expression of GAL and GALRs in different brain tumors by immunohistochemistry. Anterior pituitary gland (n = 7), pituitary adenoma (n = 9) and glioma of different WHO grades I-IV (n = 55) were analyzed for the expression of GAL and the three GALRs with antibodies recently extensively validated for specificity. While high focal GAL immunoreactivity was detected in up to 40% of cells in the anterior pituitary gland samples, only one pituitary adenoma showed focal GAL expression, at a low level. In the anterior pituitary, GAL1-R and GAL3-R protein expression was observed in up to 15% of cells, whereas receptor expression was not detected in pituitary adenoma. In glioma, diffuse and focal GAL staining was noticed in the majority of cases. GAL1-R was observed in eight out of nine glioma subtypes. GAL2-R immunoreactivity was not detected in glioma and pituitary adenoma, while GAL3-R expression was significantly associated to high-grade glioma (WHO grade IV). Most interestingly, expression of GAL and GALRs was observed in tumor-infiltrating immune cells, including neutrophils and glioma-associated macrophages/microglia. The presence of GALRs on tumor-associated immune cells, especially macrophages, indicates that GAL signaling contributes to homeostasis of the tumor microenvironment. Thus, our data indicate that GAL signaling in tumor-supportive myeloid cells could be a novel therapeutic target.

UI MeSH Term Description Entries
D008875 Middle Aged An adult aged 45 - 64 years. Middle Age
D010911 Pituitary Neoplasms Neoplasms which arise from or metastasize to the PITUITARY GLAND. The majority of pituitary neoplasms are adenomas, which are divided into non-secreting and secreting forms. Hormone producing forms are further classified by the type of hormone they secrete. Pituitary adenomas may also be characterized by their staining properties (see ADENOMA, BASOPHIL; ADENOMA, ACIDOPHIL; and ADENOMA, CHROMOPHOBE). Pituitary tumors may compress adjacent structures, including the HYPOTHALAMUS, several CRANIAL NERVES, and the OPTIC CHIASM. Chiasmal compression may result in bitemporal HEMIANOPSIA. Pituitary Cancer,Cancer of Pituitary,Cancer of the Pituitary,Pituitary Adenoma,Pituitary Carcinoma,Pituitary Tumors,Adenoma, Pituitary,Adenomas, Pituitary,Cancer, Pituitary,Cancers, Pituitary,Carcinoma, Pituitary,Carcinomas, Pituitary,Neoplasm, Pituitary,Neoplasms, Pituitary,Pituitary Adenomas,Pituitary Cancers,Pituitary Carcinomas,Pituitary Neoplasm,Pituitary Tumor,Tumor, Pituitary,Tumors, Pituitary
D001932 Brain Neoplasms Neoplasms of the intracranial components of the central nervous system, including the cerebral hemispheres, basal ganglia, hypothalamus, thalamus, brain stem, and cerebellum. Brain neoplasms are subdivided into primary (originating from brain tissue) and secondary (i.e., metastatic) forms. Primary neoplasms are subdivided into benign and malignant forms. In general, brain tumors may also be classified by age of onset, histologic type, or presenting location in the brain. Brain Cancer,Brain Metastases,Brain Tumors,Cancer of Brain,Malignant Primary Brain Tumors,Neoplasms, Intracranial,Benign Neoplasms, Brain,Brain Neoplasm, Primary,Brain Neoplasms, Benign,Brain Neoplasms, Malignant,Brain Neoplasms, Malignant, Primary,Brain Neoplasms, Primary Malignant,Brain Tumor, Primary,Brain Tumor, Recurrent,Cancer of the Brain,Intracranial Neoplasms,Malignant Neoplasms, Brain,Malignant Primary Brain Neoplasms,Neoplasms, Brain,Neoplasms, Brain, Benign,Neoplasms, Brain, Malignant,Neoplasms, Brain, Primary,Primary Brain Neoplasms,Primary Malignant Brain Neoplasms,Primary Malignant Brain Tumors,Benign Brain Neoplasm,Benign Brain Neoplasms,Benign Neoplasm, Brain,Brain Benign Neoplasm,Brain Benign Neoplasms,Brain Cancers,Brain Malignant Neoplasm,Brain Malignant Neoplasms,Brain Metastase,Brain Neoplasm,Brain Neoplasm, Benign,Brain Neoplasm, Malignant,Brain Neoplasms, Primary,Brain Tumor,Brain Tumors, Recurrent,Cancer, Brain,Intracranial Neoplasm,Malignant Brain Neoplasm,Malignant Brain Neoplasms,Malignant Neoplasm, Brain,Neoplasm, Brain,Neoplasm, Intracranial,Primary Brain Neoplasm,Primary Brain Tumor,Primary Brain Tumors,Recurrent Brain Tumor,Recurrent Brain Tumors,Tumor, Brain
D002648 Child A person 6 to 12 years of age. An individual 2 to 5 years old is CHILD, PRESCHOOL. Children
D002675 Child, Preschool A child between the ages of 2 and 5. Children, Preschool,Preschool Child,Preschool Children
D005910 Glioma Benign and malignant central nervous system neoplasms derived from glial cells (i.e., astrocytes, oligodendrocytes, and ependymocytes). Astrocytes may give rise to astrocytomas (ASTROCYTOMA) or glioblastoma multiforme (see GLIOBLASTOMA). Oligodendrocytes give rise to oligodendrogliomas (OLIGODENDROGLIOMA) and ependymocytes may undergo transformation to become EPENDYMOMA; CHOROID PLEXUS NEOPLASMS; or colloid cysts of the third ventricle. (From Escourolle et al., Manual of Basic Neuropathology, 2nd ed, p21) Glial Cell Tumors,Malignant Glioma,Mixed Glioma,Glial Cell Tumor,Glioma, Malignant,Glioma, Mixed,Gliomas,Gliomas, Malignant,Gliomas, Mixed,Malignant Gliomas,Mixed Gliomas,Tumor, Glial Cell,Tumors, Glial Cell
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D000236 Adenoma A benign epithelial tumor with a glandular organization. Adenoma, Basal Cell,Adenoma, Follicular,Adenoma, Microcystic,Adenoma, Monomorphic,Adenoma, Papillary,Adenoma, Trabecular,Adenomas,Adenomas, Basal Cell,Adenomas, Follicular,Adenomas, Microcystic,Adenomas, Monomorphic,Adenomas, Papillary,Adenomas, Trabecular,Basal Cell Adenoma,Basal Cell Adenomas,Follicular Adenoma,Follicular Adenomas,Microcystic Adenoma,Microcystic Adenomas,Monomorphic Adenoma,Monomorphic Adenomas,Papillary Adenoma,Papillary Adenomas,Trabecular Adenoma,Trabecular Adenomas
D000293 Adolescent A person 13 to 18 years of age. Adolescence,Youth,Adolescents,Adolescents, Female,Adolescents, Male,Teenagers,Teens,Adolescent, Female,Adolescent, Male,Female Adolescent,Female Adolescents,Male Adolescent,Male Adolescents,Teen,Teenager,Youths
D000328 Adult A person having attained full growth or maturity. Adults are of 19 through 44 years of age. For a person between 19 and 24 years of age, YOUNG ADULT is available. Adults

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