About this item:

279 Views | 577 Downloads

Author Notes:

Email: novazoitheranostics@gmail.com Email: raneja@gsu.edu

K.M. and S.D. carried out the major experiments, analyzed and interpreted the data, and wrote the manuscript.

A.O. performed in silico data analysis and assisted in writing the manuscript. D.C. carried out the immunoblot assays.

B.M. carried out fluorescence imaging and V.P. helped in designing some experiments.

M.G.V., M.D.R. and G.C. provided with tissue samples and helped in scoring of tissues.

S.V. performed in silico data analysis and critically revised the manuscript.

K.J. and E.A.M.J. contributed microarray and associated clinical data and critically revised the manuscript.

M.A.A. helped in scoring of tissue staining.

I.E. and E.R. critically revised the manuscript.

P.C.G.R. and R.A. conceived and designed the study and critically revised the manuscript.

All authors read and approved the final manuscript.

The authors gratefully acknowledge Dr. Beatrice Knudsen for her valuable suggestions during the course of this research.

The authors declare no competing financial interests.

Subjects:

Research Funding:

This study was supported by grants to RA from the National Cancer Institutes of Health (U01 CA179671 and R01 CA169127) and a graduate fellowship to KM from the Second Century Initiative Program at Georgia State University.

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

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

Show all authors Show less authors

Tools:

Journal Title:

Scientific Reports

Volume:

Volume 7

Publisher:

, Pages 43984-43984

Type of Work:

Article | Final Publisher PDF

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.

Copyright information:

© 2017, The Author(s)

This is an Open Access work distributed under the terms of the Creative Commons Attribution 4.0 International License (https://creativecommons.org/licenses/by/4.0/).
Export to EndNote