Amplified centrosomes and mitotic index display poor concordance between patient tumors and cultured cancer cells

作者：Mittal Karuna; Choi Da Hoon; Ogden Angela; Donthamsetty Shashi; Melton Brian D; Gupta Meenakshi V; Pannu Vaishali; Cantuaria Guilherme; Varambally Sooryanarayana; Reid Michelle D; Jonsdottir Kristin; Janssen Emiel A M; Aleskandarany Mohammad A; Ellis Ian O; Rakha Emad A; Rida Padmashree C G; Aneja Ritu

来源：Scientific Reports, 2017, 7(1): 43984.

DOI：10.1038/srep43984

Centrosome aberrations (CA) and abnormal mitoses are considered beacons of malignancy. Cancer cell doubling times in patient tumors are longer than in cultures, but differences in CA between tumors and cultured cells are uncharacterized. We compare mitoses and CA in patient tumors, xenografts, and tumor cell lines. We find that mitoses are rare in patient tumors compared with xenografts and cell lines. Contrastingly, CA is more extensive in patient tumors and xenografts (similar to 35-50% cells) than cell lines (similar to 5-15%), although CA declines in patient-derived tumor cells over time. Intratumoral hypoxia may explain elevated CA in vivo because exposure of cultured cells to hypoxia or mimicking hypoxia pharmacologically or genetically increases CA, and HIF-1 alpha and hypoxic gene signature expression correlate with CA and centrosomal gene signature expression in breast tumors. These results highlight the importance of utilizing low-passage-number patient-derived cell lines in studying CA to more faithfully recapitulate in vivo cellular phenotypes.

• 出版日期2017-3-8