Abstract
The present chapter analyses the cellular genomic status and type of cell divisions of pre-senescent cell populations shortly before the senescent phase. The purpose was to identify cellular mechanisms contributing to genomic unstable escape cells from senescence, in likeness with cancer recurrence from dormancy/remission periods. Primary diploid, human fibroblast cells were passage-extended to dysfunctional telomere-induced senescence (TAS) during which endopolyploidization occurred shortly before senescence. These cells either reduced genomic content to unstable near-diploid cells by irregular whole complement co-segregation, perpendicularly to the cytoskeleton axis or by nuclear fragmentation into multinuclear cells. The endo-division offspring-cells acquired genomic/chromosomal instability (CIN) from inheritance of endo-division traits, and gained proliferative freedom from contact inhibition by the perpendicularity of the endo-division. Other cells during this low proliferative period showed chromosomal aberrations and mitotic restitution, before a general change to senescent cells. The senescent phase showed change to typical cytoplasmic rich, amorphous flat cells, which were beta-galactosidase positive. Several types of escape mechanisms were observed (most frequent: nuclear bud-offs) which were associated with mitotic activity, albeit with limited propagation. These cells showed slight cell-shape changes from cell polarity change – a trait caused by endo-division perpendicularity. In experiments designed to simulate tumor therapy-induced genomic damage (to kill cells) endopolyploid cycling activity was increased before change to large amorphous, senescent cells. Young senescent escape-cells used the bud-off escape route, whereas escapes from old cells showed triangular cells in close contact with the senescent cells, which grew into three dimensional (3-D) tumor-like spheres. These observations were discussed as to tumor recurrence after prolonged dormancy/remission periods.
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Acknowledgement
I am very grateful to Dr. Carl Hanson of the Department of Public Health, Viral and Rickettsial Laboratory for critical comments and suggestions and to Chao Pan for computer assistance.
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Walen, K.H. (2013). Senescence Arrest of Endopolyploid Cells Renders Senescence into One Mechanism for Positive Tumorigenesis. In: Hayat, M. (eds) Tumor Dormancy, Quiescence, and Senescence, Volume 1. Tumor Dormancy and Cellular Quiescence and Senescence, vol 1. Springer, Dordrecht. https://doi.org/10.1007/978-94-007-5958-9_18
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DOI: https://doi.org/10.1007/978-94-007-5958-9_18
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