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2017 ; 8
(17
): 28769-28784
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Unsuccessful mitosis in multicellular tumour spheroids
#MMPMID28430635
Molla A
; Couvet M
; Coll JL
Oncotarget
2017[Apr]; 8
(17
): 28769-28784
PMID28430635
show ga
Multicellular spheroids are very attractive models in oncology because they mimic
the 3D organization of the tumour cells with their microenvironment. We show here
using 3 different cell types (mammary TSA/pc, embryonic kidney Hek293 and
cervical cancer HeLa), that when the cells are growing as spheroids the frequency
of binucleated cells is augmented as occurs in some human tumours.We therefore
describe mitosis in multicellular spheroids by following mitotic markers and by
time-lapse experiments. Chromosomes alignment appears to be correct on the
metaphasic plate and the passenger complex is well localized on centromere.
Moreover aurora kinases are fully active and histone H3 is phosphorylated on Ser
10. Consequently, the mitotic spindle checkpoint is satisfied and, anaphase
proceeds as illustrated by the transfer of survivin on the spindle and by the
segregation of the two lots of chromosomes. However, the segregation plane is not
well defined and oscillations of the dividing cells are observed. Finally,
cytokinesis fails and the absence of separation of the two daughter cells gives
rise to binucleated cells.Division orientation is specified during interphase and
persists throughout mitosis. Our data indicate that the cancer cells, in
multicellular spheroids, lose their ability to regulate their orientation, a
feature commonly encountered in tumours.Moreover, multicellular spheroid
expansion is still sensitive to mitotic drugs as pactlitaxel and aurora kinase
inhibitors. The spheroids thus represent a highly relevant model for studying
drug efficiency in tumours.
|*Mitosis
[MESH]
|Aurora Kinase B/*metabolism
[MESH]
|Cell Polarity
[MESH]
|Chromosome Segregation
[MESH]
|Cytokinesis
[MESH]
|HEK293 Cells
[MESH]
|HeLa Cells
[MESH]
|Histones/*metabolism
[MESH]
|Humans
[MESH]
|Inhibitor of Apoptosis Proteins/*metabolism
[MESH]
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