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

• Type of Material: Article
• Authors: Vaishali Pannu, Georgia State University; Karuna Mittal, Georgia State University; Guilherme Cantuaria, Northside Hospital; Michelle Reid, Emory University; Xiaoxian Li, Emory University; Shashikiran Donthamsetty, Georgia State University; Michelle McBride, Georgia State University; Sergey Klimov, Georgia State University; Remus Osan, Georgia State University; Meenaskhi V. Gupta, West Georgia Hospital; Padmashree C. G. Rida, Georgia State University; Ritu Aneja, Georgia State University
• Language: English
• Date: 2015-04-30
• Publisher: Impact Journals
• Publication Version: Final Published Version
• Copyright Statement: © 2015 Pannu et al.
• License: Creative Commons Attribution 4.0 International
• Final Published Version (URL): http://dx.doi.org/10.18632/oncotarget.3402
• Title of Journal or Parent Work: Oncotarget
• ISSN: 1949-2553
• Volume: 6
• Issue: 12
• Start Page: 10487
• End Page: 10497
• Grant/Funding Information: This study was supported by grants to RA from the National Cancer Institute at the National Institutes of Health (U01 CA179671, R01 CA169127).
• Keywords: ABNORMALITIES; centrosome amplification; Life Sciences & Biomedicine; Cell Biology; Oncology; CELL-CYCLE; BRCA1; ABERRATIONS; PROGRESSION; metastasis; TUMORS; RISK; INSTABILITY; disease prognosis; triple negative breast cancer; Science & Technology; CARCINOMAS
• Research Categories: Health Sciences, Oncology; Health Sciences, Pathology

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.