Universität zu Köln

Telentschak, Sergej, Soliwoda, Mark, Nohroudi, Klaus, Addicks, Klaus and Klinz, Franz-Josef (2015). Cytokinesis failure and successful multipolar mitoses drive aneuploidy in glioblastoma cells. Oncol. Rep., 33 (4). S. 2001 - 2009. ATHENS: SPANDIDOS PUBL LTD. ISSN 1791-2431

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Abstract

Glioblastoma (GB) is the most frequent human brain tumor and is associated with a poor prognosis. Multipolar mitosis and spindles have occasionally been observed in cultured glioblastoma cells and in glioblastoma tissues, but their mode of origin and relevance have remained unclear. In the present study, we investigated a novel GB cell line (SGB4) exhibiting mitotic aberrations and established a functional link between cytokinesis failure, centrosome amplification, multipolar mitosis and aneuploidy in glioblastoma. Long-term live cell imaging showed that >3% of mitotic SGB4 cells underwent multipolar mitosis (tripolar > tetrapolar > pentapolar). A significant amount of daugther cells generated by multipolar mitosis were viable and completed several rounds of mitosis. Pedigree analysis of mitotic events revealed that in many cases a bipolar mitosis with failed cytokinesis occurred prior to a multipolar mitosis. Additionally, we observed that SGB4 cells were also able to undergo a bipolar mitosis after failed cytokinesis. Colchicine-induced mitotic arrest and metaphase spreads demonstrated that SGB4 cells had a modal chromosome number of 58 ranging from 23 to 170. Approximately 82% of SGB4 cells were hyperdiploid (47-57 chromosomes) or hypotriploid (58-68 chromosomes). In conclusion, SGB4 cells passed through multipolar cell divisions and generated viable progeny by reductive mitoses. Our results identified cytokinesis failure occurring before and after multipolar or bipolar mitoses as important mechanisms to generate chromosomal heterogeneity in glioblastoma cells.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Telentschak, Sergej UNSPECIFIED UNSPECIFIED UNSPECIFIED Soliwoda, Mark UNSPECIFIED UNSPECIFIED UNSPECIFIED Nohroudi, Klaus UNSPECIFIED UNSPECIFIED UNSPECIFIED Addicks, Klaus UNSPECIFIED UNSPECIFIED UNSPECIFIED Klinz, Franz-Josef UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-403836
DOI:	10.3892/or.2015.3751
Journal or Publication Title:	Oncol. Rep.
Volume:	33
Number:	4
Page Range:	S. 2001 - 2009
Date:	2015
Publisher:	SPANDIDOS PUBL LTD
Place of Publication:	ATHENS
ISSN:	1791-2431
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language CANCER; CONSEQUENCES; PROLIFERATION; HETEROGENEITY; ABERRATIONS; INSTABILITY; MECHANISMS; KARYOTYPES; MULTIFORME; PLOIDY Multiple languages Oncology Multiple languages
URI:	http://kups.ub.uni-koeln.de/id/eprint/40383