title: Amplified centrosomes and mitotic index display poor concordance between patient tumors and cultured cancer cells.
abstract: Centrosome aberrations (CA) and abnormal mitoses are considered beacons of malignancy. Cancer cell doubling times in patient tumors are longer than in cultures, but differences in CA between tumors and cultured cells are uncharacterized. We compare mitoses and CA in patient tumors, xenografts, and tumor cell lines. We find that mitoses are rare in patient tumors compared with xenografts and cell lines. Contrastingly, CA is more extensive in patient tumors and xenografts (~35-50% cells) than cell lines (~5-15%), although CA declines in patient-derived tumor cells over time. Intratumoral hypoxia may explain elevated CA in vivo because exposure of cultured cells to hypoxia or mimicking hypoxia pharmacologically or genetically increases CA, and HIF-1α and hypoxic gene signature expression correlate with CA and centrosomal gene signature expression in breast tumors. These results highlight the importance of utilizing low-passage-number patient-derived cell lines in studying CA to more faithfully recapitulate in vivo cellular phenotypes.
authors.affiliation: Department of Biology, Georgia State University, Atlanta, GA, USA.
authors.forename: Karuna
authors.initials: K
authors.lastname: Mittal
authors.affiliation: Department of Biology, Georgia State University, Atlanta, GA, USA.
authors.forename: Da Hoon
authors.initials: DH
authors.lastname: Choi
authors.affiliation: Department of Biology, Georgia State University, Atlanta, GA, USA.
authors.forename: Angela
authors.initials: A
authors.lastname: Ogden
authors.affiliation: Department of Biology, Georgia State University, Atlanta, GA, USA.
authors.forename: Shashi
authors.initials: S
authors.lastname: Donthamsetty
authors.affiliation: Department of Biology, Georgia State University, Atlanta, GA, USA.
authors.forename: Brian D
authors.initials: BD
authors.lastname: Melton
authors.affiliation: Department of Pathology, West Georgia Hospital, Lagrange, GA, USA.
authors.forename: Meenakshi V
authors.initials: MV
authors.lastname: Gupta
authors.affiliation: Department of Biology, Georgia State University, Atlanta, GA, USA.
authors.forename: Vaishali
authors.initials: V
authors.lastname: Pannu
authors.affiliation: Department of Gynecologic Oncology, Northside Hospital Cancer Institute, Atlanta, GA, USA.
authors.forename: Guilherme
authors.initials: G
authors.lastname: Cantuaria
authors.affiliation: Department of Pathology, University of Alabama, Birmingham, AL, USA.
authors.forename: Sooryanarayana
authors.initials: S
authors.lastname: Varambally
authors.affiliation: Department of Pathology, Emory University School of Medicine, Atlanta, GA, USA.
authors.forename: Michelle D
authors.initials: MD
authors.lastname: Reid
authors.affiliation: Department of Pathology, Stavanger University Hospital, Stavanger, Norway, USA.
authors.forename: Kristin
authors.initials: K
authors.lastname: Jonsdottir
authors.affiliation: Department of Pathology, Stavanger University Hospital, Stavanger, Norway, USA.
authors.forename: Emiel A M
authors.initials: EA
authors.lastname: Janssen
authors.affiliation: Division of Cancer and Stem Cells, School of Medicine, University of Nottingham and Nottingham University Hospitals NHS Trust, City Hospital Campus, Nottingham, NG5 1PB, UK.
authors.forename: Mohammad A
authors.initials: MA
authors.lastname: Aleskandarany
authors.affiliation: Division of Cancer and Stem Cells, School of Medicine, University of Nottingham and Nottingham University Hospitals NHS Trust, City Hospital Campus, Nottingham, NG5 1PB, UK.
authors.forename: Ian O
authors.initials: IO
authors.lastname: Ellis
authors.affiliation: Division of Cancer and Stem Cells, School of Medicine, University of Nottingham and Nottingham University Hospitals NHS Trust, City Hospital Campus, Nottingham, NG5 1PB, UK.
authors.forename: Emad A
authors.initials: EA
authors.lastname: Rakha
authors.affiliation: Department of Biology, Georgia State University, Atlanta, GA, USA.|Novazoi Theranostics, Inc., Rolling Hills Estates, CA, USA.
authors.forename: Padmashree C G
authors.initials: PC
authors.lastname: Rida
authors.affiliation: Department of Biology, Georgia State University, Atlanta, GA, USA.
authors.forename: Ritu
authors.initials: R
authors.lastname: Aneja
mesh_terms: D000818:Animals; D001943:Breast Neoplasms / Q000378:metabolism / Q000473:pathology*; D064113:CRISPR-Cas Systems / Q000235:genetics; D015687:Cell Hypoxia; D045744:Cell Line, Tumor; D018385:Centrosome / Q000378:metabolism*; D005260:Female; D006801:Humans; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000235:genetics / Q000378:metabolism; D008297:Male; D051379:Mice; D008819:Mice, Nude; D008856:Microscopy, Fluorescence; D008940:Mitotic Index; D010190:Pancreatic Neoplasms / Q000378:metabolism / Q000473:pathology*; D014183:Transplantation, Heterologous; D001749:Urinary Bladder Neoplasms / Q000378:metabolism / Q000473:pathology
chemical_list: D051795:Hypoxia-Inducible Factor 1, alpha Subunit