title: Intercellular cooperation and competition in brain cancers: lessons from Drosophila and human studies.
abstract: Glioblastoma (GBM) is a primary brain cancer with an extremely poor prognosis. GBM tumors contain heterogeneous cellular components, including a small subpopulation of tumor cells termed glioma stem cells (GSCs). GSCs are characterized as chemotherapy- and radiotherapy-resistant cells with prominent tumorigenic ability. Studies in Drosophila cancer models demonstrated that interclonal cooperation and signaling from apoptotic clones provokes aggressive growth of neighboring tumorigenic clones, via compensatory proliferation or apoptosis induced proliferation. Mechanistically, these aggressive tumors depend on activation of Jun-N-terminal kinase (upstream of c-JUN), and Drosophila Wnt (Wg) in the apoptotic clones. Consistent with these nonmammalian studies, data from several mammalian studies have shown that c-JUN and Wnt are hyperactivated in aggressive tumors (including GBM). However, it remains elusive whether compensatory proliferation is an evolutionarily conserved mechanism in cancers. In the present report, we summarize recent studies in Drosophila models and mammalian models (e.g., xenografts of human cancer cells into small animals) to elucidate the intercellular interactions between the apoptosis-prone cancer cells (e.g., non-GSCs) and the hyperproliferative cancer cells (e.g., GSCs). These evolving investigations will yield insights about molecular signaling interactions in the context of post-therapeutic phenotypic changes in human cancers. Furthermore, these studies are likely to revise our understanding of the genetic changes and post-therapeutic cell-cell interactions, which is a vital area of cancer biology with wide applications to many cancer types in humans.
authors.affiliation: Center for Tissue Regeneration and Engineering at Dayton (TREND), Department of Biology, and.
authors.forename: Indrayani
authors.initials: I
authors.lastname: Waghmare
authors.affiliation: PreMedical Programs, University of Dayton, Dayton, Ohio, USA;
authors.forename: Austin
authors.initials: A
authors.lastname: Roebke
authors.affiliation: Department of Neurological Surgery and.
authors.forename: Mutsuko
authors.initials: M
authors.lastname: Minata
authors.affiliation: Center for Tissue Regeneration and Engineering at Dayton (TREND), Department of Biology, and PreMedical Programs, University of Dayton, Dayton, Ohio, USA; mkangosingh1@udayton.edu Ichiro.Nakano@osumc.edu.
authors.forename: Madhuri
authors.initials: M
authors.lastname: Kango-Singh
authors.affiliation: Department of Neurological Surgery and James Comprehensive Cancer Center, The Ohio State University, Columbus, Ohio, USA.
authors.forename: Ichiro
authors.initials: I
authors.lastname: Nakano
mesh_terms: D000818:Animals; D001932:Brain Neoplasms / Q000378:metabolism / Q000473:pathology; D029721:Drosophila Proteins / Q000378:metabolism; D004331:Drosophila melanogaster; D019008:Drug Resistance, Neoplasm; D005909:Glioblastoma / Q000378:metabolism / Q000473:pathology; D006801:Humans; D048031:JNK Mitogen-Activated Protein Kinases / Q000378:metabolism; D009363:Neoplasm Proteins / Q000378:metabolism; D009374:Neoplasms, Experimental / Q000378:metabolism / Q000473:pathology; D014411:Neoplastic Stem Cells / Q000378:metabolism / Q000473:pathology; D011836:Radiation Tolerance; D051153:Wnt Proteins / Q000378:metabolism
chemical_list: D029721:Drosophila Proteins; D009363:Neoplasm Proteins; D051153:Wnt Proteins; D048031:JNK Mitogen-Activated Protein Kinases