Adrenomedullin expression and regulation in human glioblastoma, cultured human glioblastoma cell lines and pilocytic astrocytoma. 2011

Philippe Metellus, and Brigitte Voutsinos-Porche, and Isabelle Nanni-Metellus, and Carole Colin, and Frédéric Fina, and Caroline Berenguer, and Nadège Dussault, and Françoise Boudouresque, and Anderson Loundou, and Dominique Intagliata, and Olivier Chinot, and Pierre-Marie Martin, and Dominique Figarella-Branger, and L'Houcine Ouafik
INSERM UMR 911, Faculté de Médecine Timone, 13385 Marseille, France. philippe.metellus@mail.ap-hm.fr

Clinical and experimental studies suggest that angiogenesis is a prerequisite for solid tumour growth. Glioblastoma (GBM) and pilocytic astrocytoma (PA), both angiogenic tumours display strong contrast enhancement associated with peripheral oedema in GBM but not in PA indicating differences in vascular permeability in these two types of gliomas. Here we show that expression of adrenomedullin (AM) mRNA is induced in GBM whereas is barely detectable in PA. In situ analysis of tumour specimens undergoing neovascularisation shows that the production of AM is specifically induced in a subset of GBM cells distinguished by their immediate proximity to necrotic foci (presumably hypoxic regions), suggesting a hypoxic induction of AM expression in GBM. Vascular endothelial growth factor (VEGF) mRNA levels are increased in GBM and moderate in PA. Immunohistochemical study showed that cytoplasmic AM, VEGF and HIF-1α nuclear immunoreactivity were recorded in GBM located near large necrotic areas whereas they were not expressed by PA tumour cells. Interestingly, double fluorescence immunostaining demonstrated that 85% of AM immunoreactivity colocalised with VEGF. AM transduces its effects through calcitonin receptor-like receptor/receptor activity modifying protein-2 and -3 (CLR/RAMP2 and CLR/RAMP3). Real-time quantitative RT-PCR showed expression of RAMP2, RAMP3 and CLR in PA and GBM, suggesting that AM may function as an autocrine/paracrine growth factor for GBM cells. These observations strongly support the concept that tumour angiogenesis is regulated by paracrine mechanisms and identify beside VEGF, AM as a potential tumour angiogenesis factor in vivo which constitutes a potential interesting molecular target in GBM treatment.

UI MeSH Term Description Entries
D007150 Immunohistochemistry Histochemical localization of immunoreactive substances using labeled antibodies as reagents. Immunocytochemistry,Immunogold Techniques,Immunogold-Silver Techniques,Immunohistocytochemistry,Immunolabeling Techniques,Immunogold Technics,Immunogold-Silver Technics,Immunolabeling Technics,Immunogold Silver Technics,Immunogold Silver Techniques,Immunogold Technic,Immunogold Technique,Immunogold-Silver Technic,Immunogold-Silver Technique,Immunolabeling Technic,Immunolabeling Technique,Technic, Immunogold,Technic, Immunogold-Silver,Technic, Immunolabeling,Technics, Immunogold,Technics, Immunogold-Silver,Technics, Immunolabeling,Technique, Immunogold,Technique, Immunogold-Silver,Technique, Immunolabeling,Techniques, Immunogold,Techniques, Immunogold-Silver,Techniques, Immunolabeling
D008856 Microscopy, Fluorescence Microscopy of specimens stained with fluorescent dye (usually fluorescein isothiocyanate) or of naturally fluorescent materials, which emit light when exposed to ultraviolet or blue light. Immunofluorescence microscopy utilizes antibodies that are labeled with fluorescent dye. Fluorescence Microscopy,Immunofluorescence Microscopy,Microscopy, Immunofluorescence,Fluorescence Microscopies,Immunofluorescence Microscopies,Microscopies, Fluorescence,Microscopies, Immunofluorescence
D009389 Neovascularization, Pathologic A pathologic process consisting of the proliferation of blood vessels in abnormal tissues or in abnormal positions. Angiogenesis, Pathologic,Angiogenesis, Pathological,Neovascularization, Pathological,Pathologic Angiogenesis,Pathologic Neovascularization,Pathological Angiogenesis,Pathological Neovascularization
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
D005909 Glioblastoma A malignant form of astrocytoma histologically characterized by pleomorphism of cells, nuclear atypia, microhemorrhage, and necrosis. They may arise in any region of the central nervous system, with a predilection for the cerebral hemispheres, basal ganglia, and commissural pathways. Clinical presentation most frequently occurs in the fifth or sixth decade of life with focal neurologic signs or seizures. Astrocytoma, Grade IV,Giant Cell Glioblastoma,Glioblastoma Multiforme,Astrocytomas, Grade IV,Giant Cell Glioblastomas,Glioblastoma, Giant Cell,Glioblastomas,Glioblastomas, Giant Cell,Grade IV Astrocytoma,Grade IV Astrocytomas
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D000860 Hypoxia Sub-optimal OXYGEN levels in the ambient air of living organisms. Anoxia,Oxygen Deficiency,Anoxemia,Deficiency, Oxygen,Hypoxemia,Deficiencies, Oxygen,Oxygen Deficiencies
D001254 Astrocytoma Neoplasms of the brain and spinal cord derived from glial cells which vary from histologically benign forms to highly anaplastic and malignant tumors. Fibrillary astrocytomas are the most common type and may be classified in order of increasing malignancy (grades I through IV). In the first two decades of life, astrocytomas tend to originate in the cerebellar hemispheres; in adults, they most frequently arise in the cerebrum and frequently undergo malignant transformation. (From Devita et al., Cancer: Principles and Practice of Oncology, 5th ed, pp2013-7; Holland et al., Cancer Medicine, 3d ed, p1082) Astrocytoma, Subependymal Giant Cell,Glioma, Astrocytic,Oligoastrocytoma, Mixed,Pleomorphic Xanthoastrocytomas,Anaplastic Astrocytoma,Astrocytoma, Grade I,Astrocytoma, Grade II,Astrocytoma, Grade III,Astrocytoma, Protoplasmic,Astroglioma,Cerebral Astrocytoma,Childhood Cerebral Astrocytoma,Fibrillary Astrocytoma,Gemistocytic Astrocytoma,Intracranial Astrocytoma,Juvenile Pilocytic Astrocytoma,Pilocytic Astrocytoma,Subependymal Giant Cell Astrocytoma,Anaplastic Astrocytomas,Astrocytic Glioma,Astrocytic Gliomas,Astrocytoma, Anaplastic,Astrocytoma, Cerebral,Astrocytoma, Childhood Cerebral,Astrocytoma, Fibrillary,Astrocytoma, Gemistocytic,Astrocytoma, Intracranial,Astrocytoma, Juvenile Pilocytic,Astrocytoma, Pilocytic,Astrocytomas,Astrocytomas, Grade III,Astrogliomas,Cerebral Astrocytoma, Childhood,Cerebral Astrocytomas,Childhood Cerebral Astrocytomas,Fibrillary Astrocytomas,Gemistocytic Astrocytomas,Gliomas, Astrocytic,Grade I Astrocytoma,Grade I Astrocytomas,Grade II Astrocytoma,Grade II Astrocytomas,Grade III Astrocytoma,Grade III Astrocytomas,Intracranial Astrocytomas,Juvenile Pilocytic Astrocytomas,Mixed Oligoastrocytoma,Mixed Oligoastrocytomas,Pilocytic Astrocytoma, Juvenile,Pilocytic Astrocytomas,Pleomorphic Xanthoastrocytoma,Protoplasmic Astrocytoma,Protoplasmic Astrocytomas,Xanthoastrocytoma, Pleomorphic
D015972 Gene Expression Regulation, Neoplastic Any of the processes by which nuclear, cytoplasmic, or intercellular factors influence the differential control of gene action in neoplastic tissue. Neoplastic Gene Expression Regulation,Regulation of Gene Expression, Neoplastic,Regulation, Gene Expression, Neoplastic
D017403 In Situ Hybridization A technique that localizes specific nucleic acid sequences within intact chromosomes, eukaryotic cells, or bacterial cells through the use of specific nucleic acid-labeled probes. Hybridization in Situ,Hybridization, In Situ,Hybridizations, In Situ,In Situ Hybridizations

Related Publications

Philippe Metellus, and Brigitte Voutsinos-Porche, and Isabelle Nanni-Metellus, and Carole Colin, and Frédéric Fina, and Caroline Berenguer, and Nadège Dussault, and Françoise Boudouresque, and Anderson Loundou, and Dominique Intagliata, and Olivier Chinot, and Pierre-Marie Martin, and Dominique Figarella-Branger, and L'Houcine Ouafik
March 2021, General physiology and biophysics,
Philippe Metellus, and Brigitte Voutsinos-Porche, and Isabelle Nanni-Metellus, and Carole Colin, and Frédéric Fina, and Caroline Berenguer, and Nadège Dussault, and Françoise Boudouresque, and Anderson Loundou, and Dominique Intagliata, and Olivier Chinot, and Pierre-Marie Martin, and Dominique Figarella-Branger, and L'Houcine Ouafik
April 2014, Brain tumor pathology,
Philippe Metellus, and Brigitte Voutsinos-Porche, and Isabelle Nanni-Metellus, and Carole Colin, and Frédéric Fina, and Caroline Berenguer, and Nadège Dussault, and Françoise Boudouresque, and Anderson Loundou, and Dominique Intagliata, and Olivier Chinot, and Pierre-Marie Martin, and Dominique Figarella-Branger, and L'Houcine Ouafik
December 1996, Journal of neuro-oncology,
Philippe Metellus, and Brigitte Voutsinos-Porche, and Isabelle Nanni-Metellus, and Carole Colin, and Frédéric Fina, and Caroline Berenguer, and Nadège Dussault, and Françoise Boudouresque, and Anderson Loundou, and Dominique Intagliata, and Olivier Chinot, and Pierre-Marie Martin, and Dominique Figarella-Branger, and L'Houcine Ouafik
January 1997, Neurochemistry international,
Philippe Metellus, and Brigitte Voutsinos-Porche, and Isabelle Nanni-Metellus, and Carole Colin, and Frédéric Fina, and Caroline Berenguer, and Nadège Dussault, and Françoise Boudouresque, and Anderson Loundou, and Dominique Intagliata, and Olivier Chinot, and Pierre-Marie Martin, and Dominique Figarella-Branger, and L'Houcine Ouafik
November 2000, Journal of neurochemistry,
Philippe Metellus, and Brigitte Voutsinos-Porche, and Isabelle Nanni-Metellus, and Carole Colin, and Frédéric Fina, and Caroline Berenguer, and Nadège Dussault, and Françoise Boudouresque, and Anderson Loundou, and Dominique Intagliata, and Olivier Chinot, and Pierre-Marie Martin, and Dominique Figarella-Branger, and L'Houcine Ouafik
May 2001, Neuroscience letters,
Philippe Metellus, and Brigitte Voutsinos-Porche, and Isabelle Nanni-Metellus, and Carole Colin, and Frédéric Fina, and Caroline Berenguer, and Nadège Dussault, and Françoise Boudouresque, and Anderson Loundou, and Dominique Intagliata, and Olivier Chinot, and Pierre-Marie Martin, and Dominique Figarella-Branger, and L'Houcine Ouafik
March 1996, Clinical and diagnostic laboratory immunology,
Philippe Metellus, and Brigitte Voutsinos-Porche, and Isabelle Nanni-Metellus, and Carole Colin, and Frédéric Fina, and Caroline Berenguer, and Nadège Dussault, and Françoise Boudouresque, and Anderson Loundou, and Dominique Intagliata, and Olivier Chinot, and Pierre-Marie Martin, and Dominique Figarella-Branger, and L'Houcine Ouafik
March 1997, Journal of neuropathology and experimental neurology,
Philippe Metellus, and Brigitte Voutsinos-Porche, and Isabelle Nanni-Metellus, and Carole Colin, and Frédéric Fina, and Caroline Berenguer, and Nadège Dussault, and Françoise Boudouresque, and Anderson Loundou, and Dominique Intagliata, and Olivier Chinot, and Pierre-Marie Martin, and Dominique Figarella-Branger, and L'Houcine Ouafik
January 2009, The Journal of steroid biochemistry and molecular biology,
Philippe Metellus, and Brigitte Voutsinos-Porche, and Isabelle Nanni-Metellus, and Carole Colin, and Frédéric Fina, and Caroline Berenguer, and Nadège Dussault, and Françoise Boudouresque, and Anderson Loundou, and Dominique Intagliata, and Olivier Chinot, and Pierre-Marie Martin, and Dominique Figarella-Branger, and L'Houcine Ouafik
January 1994, Advances in experimental medicine and biology,
Copied contents to your clipboard!