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

Abstract

// Vaishali Pannu 1 , Karuna Mittal 1 , Guilherme Cantuaria 2 , Michelle D. Reid 3 , Xiaoxian Li 3 , Shashikiran Donthamsetty 1 , Michelle McBride 1 , Sergey Klimov 1 , Remus Osan 4, 5 , Meenakshi V. Gupta 6 , Padmashree C.G. Rida 1 , Ritu Aneja 1, 7 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 Correspondence to: Padmashree C.G. Rida, e-mail: cgp_rida@yahoo.com Ritu Aneja, e-mail: raneja@gsu.edu 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.