TY - JOUR
T1 - Effects of cell death-induced proliferation on a cell competition system
AU - Nishikawa, S.
AU - Takamatsu, A.
N1 - Funding Information:
This work was supported by Japan Society for the Promotion of Science (JSPS) Grant-in-Aid for Scientific Research on Innovative Areas [grant number 26114001 ]. The sponsor had no role in study design; in the collection, analysis and interpretation of data; in the writing of the report; and in the decision to submit the article for publication.
Publisher Copyright:
© 2019 Elsevier Inc.
PY - 2019/10
Y1 - 2019/10
N2 - Cell death–induced proliferation (CDIP) is a phenomenon in which cell death activates neighboring cells and promotes their proliferation. It was first reported as “compensatory proliferation” in injured tissues, which functions to maintain normal tissues. On the other hand, this phenomenon also affects potentially tumorigenic mutant cells and promotes tumorigenesis. This discrepancy may complicate the understanding of a phenomenon called “cell competition” observed in a system consisting of wild-type (WT) cells and mutant cells in a single-layer tissue. In this system, the WT cells induce cell death in the adjacent mutant cells to eliminate them. Therefore, it is believed that CDIP serves WT cells by compensating the space previously occupied by mutant cells. On the other hand, CDIP may contribute to the expansion of a potentially tumorigenic mutant clone because this clone activates itself. With the aim to investigate the role of CDIP in cell competition, a mathematical model was constructed here by introducing a CDIP effect into the population-based cell competition model that was proposed in our previous work. In contrast to the above-mentioned first expectation, the model suggests that the CDIP of WT cells that is derived from cell competition does not affect the fate whether it follows formation of normal tissue or overgrowth of a mutant clone after cell competition. It should be noted, however, that CDIP accelerates the speed of normal tissue formation; only this point is in agreement with our expectations. In contrast, the CDIP of mutant cells that is derived from either autonomous cell death or cell competition helps mutant cells to survive.
AB - Cell death–induced proliferation (CDIP) is a phenomenon in which cell death activates neighboring cells and promotes their proliferation. It was first reported as “compensatory proliferation” in injured tissues, which functions to maintain normal tissues. On the other hand, this phenomenon also affects potentially tumorigenic mutant cells and promotes tumorigenesis. This discrepancy may complicate the understanding of a phenomenon called “cell competition” observed in a system consisting of wild-type (WT) cells and mutant cells in a single-layer tissue. In this system, the WT cells induce cell death in the adjacent mutant cells to eliminate them. Therefore, it is believed that CDIP serves WT cells by compensating the space previously occupied by mutant cells. On the other hand, CDIP may contribute to the expansion of a potentially tumorigenic mutant clone because this clone activates itself. With the aim to investigate the role of CDIP in cell competition, a mathematical model was constructed here by introducing a CDIP effect into the population-based cell competition model that was proposed in our previous work. In contrast to the above-mentioned first expectation, the model suggests that the CDIP of WT cells that is derived from cell competition does not affect the fate whether it follows formation of normal tissue or overgrowth of a mutant clone after cell competition. It should be noted, however, that CDIP accelerates the speed of normal tissue formation; only this point is in agreement with our expectations. In contrast, the CDIP of mutant cells that is derived from either autonomous cell death or cell competition helps mutant cells to survive.
KW - Compensatory proliferation
KW - Drosophila
KW - Group fitness
KW - Population model
KW - Tissue size control
KW - Tumor suppression
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U2 - 10.1016/j.mbs.2019.108241
DO - 10.1016/j.mbs.2019.108241
M3 - Article
C2 - 31449892
AN - SCOPUS:85071456191
VL - 316
JO - Mathematical Biosciences
JF - Mathematical Biosciences
SN - 0025-5564
M1 - 108241
ER -