title: Detection of primary cilia in human glioblastoma.
abstract: Glioblastoma (GBM) is the most common malignant adult brain tumor and carries a poor prognosis due to primary and acquired resistance. While many cellular features of GBM have been documented, it is unclear if cells within these tumors extend a primary cilium, an organelle whose associated signaling pathways may regulate proliferation, migration, and survival of neural precursor and tumor cells. Using immunohistochemical and electron microscopy (EM) techniques, we screened human GBM tumor biopsies and primary cell lines for cilia. Immunocytochemical staining of five primary GBM cell lines revealed that between 8 and 25 % of the cells in each line possessed gamma tubulin-positive basal bodies from which extended acetylated, alpha-tubulin-positive axonemes. EM analyses confirmed the presence of cilia at the cell surface and revealed that their axonemes contained organized networks of microtubules, a structural feature consistent with our detection of IFT88 and Arl13b, two trafficked cilia proteins, along the lengths of the axonemes. Notably, cilia were detected in each of 23 tumor biopsies (22 primary and 1 recurrent) examined. These cilia were distributed across the tumor landscape including regions proximal to the vasculature and within necrotic areas. Moreover, ciliated cells within these tumors co-stained with Ki67, a marker for actively dividing cells, and ZEB1, a transcription factor that is upregulated in GBM and linked to tumor initiation, invasion, and chemoresistance. Collectively, our data show that subpopulations of cells within human GBM tumors are ciliated. In view of mounting evidence supporting roles of primary cilia in tumor initiation and propagation, it is likely that further study of the effects of cilia on GBM tumor cell function will improve our understanding of GBM pathogenesis and may provide new directions for GBM treatment strategies.
authors: Department of Neuroscience, McKnight Brain Institute, University of Florida College of Medicine, Gainesville, FL, 32610, USA, msarkisian@ufl.edu.
authors: Matthew R
authors: MR
authors: Sarkisian
authors: Dorit
authors: D
authors: Siebzehnrubl
authors: Lan
authors: L
authors: Hoang-Minh
authors: Loic
authors: L
authors: Deleyrolle
authors: Daniel J
authors: DJ
authors: Silver
authors: Florian A
authors: FA
authors: Siebzehnrubl
authors: Sarah M
authors: SM
authors: Guadiana
authors: Gayathri
authors: G
authors: Srivinasan
authors: Susan
authors: S
authors: Semple-Rowland
authors: Jeffrey K
authors: JK
authors: Harrison
authors: Dennis A
authors: DA
authors: Steindler
authors: Brent A
authors: BA
authors: Reynolds
mesh_terms: D020727:ADP-Ribosylation Factors / Q000378:metabolism; D000369:Aged, 80 and over; D054468:Axoneme / Q000378:metabolism / Q000648:ultrastructure; D064652:Basal Bodies / Q000378:metabolism / Q000648:ultrastructure; D001932:Brain Neoplasms / Q000378:metabolism* / Q000648:ultrastructure*; D045744:Cell Line, Tumor; D002923:Cilia / Q000378:metabolism / Q000648:ultrastructure*; D005909:Glioblastoma / Q000378:metabolism* / Q000648:ultrastructure*; D018398:Homeodomain Proteins / Q000378:metabolism; D006801:Humans; D007150:Immunohistochemistry; D019394:Ki-67 Antigen / Q000378:metabolism; D008297:Male; D008854:Microscopy, Electron; D008875:Middle Aged; D014157:Transcription Factors / Q000378:metabolism; D014404:Tubulin / Q000378:metabolism; D025521:Tumor Suppressor Proteins / Q000378:metabolism; D000071799:Zinc Finger E-box-Binding Homeobox 1
chemical_list: D018398:Homeodomain Proteins; C098623:IFT88 protein, human; D019394:Ki-67 Antigen; D014157:Transcription Factors; D014404:Tubulin; D025521:Tumor Suppressor Proteins; C486307:ZEB1 protein, human; D000071799:Zinc Finger E-box-Binding Homeobox 1; D020727:ADP-Ribosylation Factors; C530391:ARL13B protein, human