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

• Published in: Oncotarget 2015-04, Vol.6 (12), p.10487-10497
• Main Authors: Pannu, Vaishali, Mittal, Karuna, Cantuaria, Guilherme, Reid, Michelle D, Li, Xiaoxian, Donthamsetty, Shashikiran, McBride, Michelle, Klimov, Sergey, Osan, Remus, Gupta, Meenakshi V, Rida, Padmashree C G, Aneja, Ritu
• Format: Article
• Language: English
• Subjects: Cell Line, Tumor; Cell Movement - physiology; Centrosome - metabolism; Disease Progression; Female; Humans; Immunohistochemistry; MCF-7 Cells; Research Paper; Survival Rate; Triple Negative Breast Neoplasms - genetics; Triple Negative Breast Neoplasms - metabolism; Triple Negative Breast Neoplasms - pathology
• ISSN: 1949-2553; 1949-2553
• DOI: 10.18632/oncotarget.3402

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.