Amplified centrosomes and mitotic index display poor concordance between patient tumors and cultured cancer cells

• Authors: Karuna Mittal, Georgia State University; Da Hoon Choi, Georgia State University; Angela Ogden, Georgia State University; Shashi Donthamsetty, Georgia State University; Brian D. Melton, Georgia State University; Meenakshi V. Gupta, West Georgia Hospital; Vaishali Pannu, Georgia State University; Guilherme Cantuaria, Northside Hospital Cancer Institute; Sooryanarayana Varambally, University of Alabama; Michelle Reid, Emory University; Kristin Jonsdottir, Stavanger University Hospital; Emiel A. M. Janssen, Stavanger University Hospital; Mohammad A. Aleskandarany, University of Nottingham; Ian O. Ellis, University of Nottingham; Emad A. Rakha, University of Nottingham; Padmashree C. G. Rida, Georgia State University; Ritu Aneja, Georgia State University
• Journal Title: Scientific Reports
• Volume: Volume 7
• Publisher: Nature Publishing Group: Open Access Journals - Option C | 2017-03-08, Pages 43984-43984
• Type of Work: Article | Final Publisher PDF
• Publisher DOI: http://doi.org/10.1038/srep43984
• Subjects: Health Sciences, Oncology; Health Sciences, Pathology; Biology, Cell
• Keywords: Science & Technology; Multidisciplinary Sciences; Science & Technology - Other Topics; HYPOXIA-INDUCIBLE FACTOR-1; AGGRESSIVE DISEASE COURSE; EXTRA-CENTROSOMES; IN-VIVO; SUPERNUMERARY CENTROSOMES; CHROMOSOMAL INSTABILITY; BREAST CANCERS; DNA-DAMAGE; AMPLIFICATION; INHIBITOR

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.