摘要
In cell cultures monolayered cell growth is controlled by contact inhibition which again is controlled by the cell polarity system by always being positioned in accord with the cytoskeleton axis. Presently, cycling endopolyploid cells (tetraploidy) were shown to undergo perpendicular divisions relative to the cytoskeleton axis which disrupted to some degree contact inhibition in the near-senescent phase of human primary cells. These experiments included genome damage-induced endopolyploidization (TAS-treated) to simulate as a model system the state of in vivo accelerated cell senescence (ACS) which is induced by therapy-associated genomic damage. From ACS delayed tumor re-growth (re-lapse) occurs from “robust” cell propagation, but mechanisms for such cell escape from senescence are unknown. For TAS-treated a karyoplast bud-off process with change to limited mitotic activity occurred in young senescent cultures. In old, deep senescent (5 - 8 weeks) cultures, unexpectedly escape cell-growth showed three dimensional (3-D) tumor-like spheres from growths of morphologically different cells as compared to the fibroblastic phenotype. These cells expressed cell polarity change, and very condensed nuclei were variously perpendicularly oriented to what-ever cell polarity was present. These results were discussed in regard to in vivo relapse and, to the importance of cell polarity change in tumorigenesis. Induced senescence as an anti-tumor mechanism in therapy treatment becomes a questionable procedure from the present experimental results.
In cell cultures monolayered cell growth is controlled by contact inhibition which again is controlled by the cell polarity system by always being positioned in accord with the cytoskeleton axis. Presently, cycling endopolyploid cells (tetraploidy) were shown to undergo perpendicular divisions relative to the cytoskeleton axis which disrupted to some degree contact inhibition in the near-senescent phase of human primary cells. These experiments included genome damage-induced endopolyploidization (TAS-treated) to simulate as a model system the state of in vivo accelerated cell senescence (ACS) which is induced by therapy-associated genomic damage. From ACS delayed tumor re-growth (re-lapse) occurs from “robust” cell propagation, but mechanisms for such cell escape from senescence are unknown. For TAS-treated a karyoplast bud-off process with change to limited mitotic activity occurred in young senescent cultures. In old, deep senescent (5 - 8 weeks) cultures, unexpectedly escape cell-growth showed three dimensional (3-D) tumor-like spheres from growths of morphologically different cells as compared to the fibroblastic phenotype. These cells expressed cell polarity change, and very condensed nuclei were variously perpendicularly oriented to what-ever cell polarity was present. These results were discussed in regard to in vivo relapse and, to the importance of cell polarity change in tumorigenesis. Induced senescence as an anti-tumor mechanism in therapy treatment becomes a questionable procedure from the present experimental results.
