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Oncotarget. 2015 Apr 30;6(12):10487-97.

Rampant centrosome amplification underlies more aggressive disease course of triple negative breast cancers.

Author information

1
Department of Biology, Georgia State University, Atlanta, GA 30303, USA.
2
Department of Gynecologic Oncology, Northside Hospital Cancer Institute, Atlanta, GA 30342, USA.
3
Department of Pathology, Emory University Hospital, Atlanta, GA 30322, USA.
4
Department of Mathematics and Statistics, Georgia State University, Atlanta, GA 30303, USA.
5
Neuroscience Institute, Georgia State University, Atlanta, GA 30303, USA.
6
Clinical Pathology & Anatomic Pathology, West Georgia Hospitals, LaGrange, GA 30240, USA.
7
Institute of Biomedical Sciences, Georgia State University, Atlanta, GA 30303, USA.

Abstract

Centrosome amplification (CA), a cell-biological trait, characterizes pre-neoplastic and pre-invasive lesions and is associated with tumor aggressiveness. Recent studies suggest that CA leads to malignant transformation and promotes invasion in mammary epithelial cells. Triple negative breast cancer (TNBC), a histologically-aggressive subtype shows high recurrence, metastases, and mortality rates. Since TNBC and non-TNBC follow variable kinetics of metastatic progression, they constitute a novel test bed to explore if severity and nature of CA can distinguish them apart. We quantitatively assessed structural and numerical centrosomal aberrations for each patient sample in a large-cohort of grade-matched TNBC (n = 30) and non-TNBC (n = 98) cases employing multi-color confocal imaging. Our data establish differences in incidence and severity of CA between TNBC and non-TNBC cell lines and clinical specimens. We found strong correlation between CA and aggressiveness markers associated with metastasis in 20 pairs of grade-matched TNBC and non-TNBC specimens (p < 0.02). Time-lapse imaging of MDA-MB-231 cells harboring amplified centrosomes demonstrated enhanced migratory ability. Our study bridges a vital knowledge gap by pinpointing that CA underlies breast cancer aggressiveness. This previously unrecognized organellar inequality at the centrosome level may allow early-risk prediction and explain higher tumor aggressiveness and mortality rates in TNBC patients.

KEYWORDS:

centrosome amplification; disease prognosis; metastasis; triple negative breast cancer

PMID:
25868856
PMCID:
PMC4496369
DOI:
10.18632/oncotarget.3402
[Indexed for MEDLINE]
Free PMC Article

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