title: Calcium signaling orchestrates glioblastoma development: Facts and conjunctures.
abstract: While it is a relatively rare disease, glioblastoma multiform (GBM) is one of the more deadly adult cancers. Following current interventions, the tumor is never eliminated whatever the treatment performed; whether it is radiotherapy, chemotherapy, or surgery. One hypothesis to explain this poor outcome is the "cancer stem cell" hypothesis. This concept proposes that a minority of cells within the tumor mass share many of the properties of adult neural stem cells and it is these that are responsible for the growth of the tumor and its resistance to existing therapies. Accumulating evidence suggests that Ca(2+) might also be an important positive regulator of tumorigenesis in GBM, in processes involving quiescence, maintenance, proliferation, or migration. Glioblastoma tumors are generally thought to develop by co-opting pathways that are involved in the formation of an organ. We propose that the cells initiating the tumor, and subsequently the cells of the tumor mass, must hijack the different checkpoints that evolution has selected in order to prevent the pathological development of an organ. In this article, two main points are discussed. (i) The first is the establishment of a so-called "cellular society," which is required to create a favorable microenvironment. (ii) The second is that GBM can be considered to be an organism, which fights to survive and develop. Since GBM evolves in a limited space, its only chance of development is to overcome the evolutionary checkpoints. For example, the deregulation of the normal Ca(2+) signaling elements contributes to the progression of the disease. Thus, by manipulating the Ca(2+) signaling, the GBM cells might not be killed, but might be reprogrammed toward a new fate that is either easy to cure or that has no aberrant functioning. This article is part of a Special Issue entitled: Calcium and Cell Fate. Guest Editors: Jacques Haiech, Claus Heizmann, Joachim Krebs, Thierry Capiod and Olivier Mignen.
authors.affiliation: Centre de Biologie du Développement, Université Toulouse 3, 118 route de Narbonne, F31062 Toulouse, Cedex 04, France; CNRS UMR5547, Toulouse F31062, France. Electronic address: catherine.leclerc@univ-tlse3.fr.
authors.forename: Catherine
authors.initials: C
authors.lastname: Leclerc
authors.affiliation: Laboratoire d'Innovation Thérapeutique, Laboratoire d'Excellence Médalis, UMR 7200 Université de Strasbourg / CNRS, 67412 Illkirch, France.
authors.forename: Jacques
authors.initials: J
authors.lastname: Haeich
authors.affiliation: Centre de Biologie du Développement, Université Toulouse 3, 118 route de Narbonne, F31062 Toulouse, Cedex 04, France.
authors.forename: Francisco J
authors.initials: FJ
authors.lastname: Aulestia
authors.affiliation: Laboratoire d'Innovation Thérapeutique, Laboratoire d'Excellence Médalis, UMR 7200 Université de Strasbourg / CNRS, 67412 Illkirch, France.
authors.forename: Marie-Claude
authors.initials: MC
authors.lastname: Kilhoffer
authors.affiliation: Division of Life Science and State Key Laboratory of Molecular Neuroscience, HKUST, Clear Water Bay, Hong Kong, PR China.
authors.forename: Andrew L
authors.initials: AL
authors.lastname: Miller
authors.affiliation: Centre de Biologie du Développement, Université Toulouse 3, 118 route de Narbonne, F31062 Toulouse, Cedex 04, France; CNRS UMR5547, Toulouse F31062, France.
authors.forename: Isabelle
authors.initials: I
authors.lastname: Néant
authors.affiliation: Division of Life Science and State Key Laboratory of Molecular Neuroscience, HKUST, Clear Water Bay, Hong Kong, PR China.
authors.forename: Sarah E
authors.initials: SE
authors.lastname: Webb
authors.affiliation: IREBS UMR7242 ESBS, Pôle API, Parc d'Innovation d'Illkirch, 67412 Illkirch cedex, France.
authors.forename: Etienne
authors.initials: E
authors.lastname: Schaeffer
authors.affiliation: Sorbonne Universités, UPMC Univ Paris 06, Centre National de la Recherche Scientifique (CNRS), UMR8246, Institut National de la Santé et de la Recherche Medicale (INSERM), U1130, Institut de Biologie Paris Seine (IBPS), Neuroscience Paris Seine (NPS), Team Glial Plasticity, 7/9 Quai St Bernard, Paris, France.
authors.forename: Marie-Pierre
authors.initials: MP
authors.lastname: Junier
authors.affiliation: Sorbonne Universités, UPMC Univ Paris 06, Centre National de la Recherche Scientifique (CNRS), UMR8246, Institut National de la Santé et de la Recherche Medicale (INSERM), U1130, Institut de Biologie Paris Seine (IBPS), Neuroscience Paris Seine (NPS), Team Glial Plasticity, 7/9 Quai St Bernard, Paris, France.
authors.forename: Hervé
authors.initials: H
authors.lastname: Chneiweiss
authors.affiliation: Centre de Biologie du Développement, Université Toulouse 3, 118 route de Narbonne, F31062 Toulouse, Cedex 04, France; CNRS UMR5547, Toulouse F31062, France.
authors.forename: Marc
authors.initials: M
authors.lastname: Moreau
mesh_terms: D000818:Animals; D002118:Calcium / Q000378:metabolism*; D020013:Calcium Signaling; D049109:Cell Proliferation / Q000235:genetics; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D005909:Glioblastoma / Q000235:genetics / Q000378:metabolism* / Q000628:therapy; D006801:Humans; D014411:Neoplastic Stem Cells / Q000378:metabolism* / Q000473:pathology; D059016:Tumor Microenvironment / Q000235:genetics
chemical_list: D002118:Calcium
keywords: Calcium signaling; Cancer stem cells; Cell competition; Glioblastoma; Inflammation; Migration; Proliferation; Quiescence