Oncotarget

Research Papers:

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

Vaishali Pannu, Karuna Mittal, Guilherme Cantuaria, Michelle D. Reid, Xiaoxian Li, Shashikiran Donthamsetty, Michelle McBride, Sergey Klimov, Remus Osan, Meenakshi V. Gupta, Padmashree C.G. Rida and Ritu Aneja _

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Oncotarget. 2015; 6:10487-10497. https://doi.org/10.18632/oncotarget.3402

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Abstract

Vaishali Pannu1, Karuna Mittal1, Guilherme Cantuaria2, Michelle D. Reid3, Xiaoxian Li3, Shashikiran Donthamsetty1, Michelle McBride1, Sergey Klimov1, Remus Osan4,5, Meenakshi V. Gupta6, Padmashree C.G. Rida1, Ritu Aneja1,7

1Department of Biology, Georgia State University, Atlanta, GA 30303, USA

2Department of Gynecologic Oncology, Northside Hospital Cancer Institute, Atlanta, GA 30342, USA

3Department of Pathology, Emory University Hospital, Atlanta, GA 30322, USA

4Department of Mathematics and Statistics, Georgia State University, Atlanta, GA 30303, USA

5Neuroscience Institute, Georgia State University, Atlanta, GA 30303, USA

6Clinical Pathology & Anatomic Pathology, West Georgia Hospitals, LaGrange, GA 30240, USA

7Institute of Biomedical Sciences, Georgia State University, Atlanta, GA 30303, USA

Correspondence to:

Padmashree C.G. Rida, e-mail: [email protected]

Ritu Aneja, e-mail: [email protected]

Keywords: centrosome amplification, triple negative breast cancer, metastasis, disease prognosis

Received: January 21, 2015     Accepted: February 16, 2015     Published: March 19, 2015

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.


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