Evidence of asymmetric cell division and centrosome inheritance in human neuroblastoma cells.
Asymmetric cell division (ACD) is believed to be a physiological event that occurs during development and tissue homeostasis in a large variety of organisms. ACD produces two unequal daughter cells, one of which resembles a multipotent stem and/or progenitor cell, whereas the other has potential for differentiation. Although recent studies have shown that the balance between self-renewal and differentiation potentials is precisely controlled and that alterations in the balance may lead to tumorigenesis in Drosophila neuroblasts, it is largely unknown whether human cancer cells directly show ACD in an evolutionarily conserved manner. Here, we show that the conserved polarity/spindle protein NuMA is preferentially localized to one side of the cell cortex during cell division, generating unequal inheritance of fate-altering molecules in human neuroblastoma cell lines. We also show that the cells with a single copy of MYCN showed significantly higher percentages of ACD than those with MYCN amplification. Moreover, suppression of MYCN in MYCN-amplified cells caused ACD, whereas expression of MYCN in MYCN-nonamplified cells enhanced symmetric cell division. Furthermore, we demonstrate that centrosome inheritance follows a definite rule in ACD: The daughter centrosome with younger mother centriole is inherited to the daughter cell with NuMA preferentially localized to the cell cortex, whereas the mother centrosome with the older mother centriole migrates to the other daughter cell. Thus, the mechanisms of cell division of ACD or symmetric cell division and centrosome inheritance are recapitulated in human cancer cells, and these findings may facilitate studies on cancer stem cells.
Division of Cancer Diagnosis, Research Institute for Clinical Oncology, Saitama Cancer Center, Ina, Saitama 362-0806, Japan. hideki@cancer-c.pref.saitama.jp
Hideki
H
Izumi
Yasuhiko
Y
Kaneko
D002455:Cell Division; D045744:Cell Line, Tumor; D018385:Centrosome; D055785:Gene Knockdown Techniques; D016259:Genes, myc; D006801:Humans; D009447:Neuroblastoma / Q000235:genetics / Q000473:pathology*