Department of Electrical Engineering and Bioscience, Waseda University, Shinjuku-ku, Tokyo 169-8555, Japan.
Department of Electrical Engineering and Bioscience, Waseda University, Shinjuku-ku, Tokyo 169-8555, Japan.
Math Biosci. 2019 Oct;316:108241. doi: 10.1016/j.mbs.2019.108241. Epub 2019 Aug 23.
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.
细胞死亡诱导的增殖（CDIP）是一种细胞死亡激活邻近细胞并促进其增殖的现象。它最初在受伤组织中被报道为“代偿性增殖”，其功能是维持正常组织。另一方面，这种现象也会影响潜在的致瘤突变细胞并促进肿瘤发生。这种差异可能会使观察到的单层组织中野生型（WT）细胞和突变细胞之间的“细胞竞争”现象的理解复杂化。在这个系统中，WT 细胞诱导相邻的突变细胞死亡以将其消除。因此，人们认为 CDIP 通过补偿突变细胞先前占据的空间来为 WT 细胞提供服务。另一方面，CDIP 可能有助于潜在致瘤突变克隆的扩张，因为该克隆会自我激活。为了研究 CDIP 在细胞竞争中的作用，我们在这里通过将 CDIP 效应引入我们之前工作中提出的基于群体的细胞竞争模型，构建了一个数学模型。与上述第一个预期相反，该模型表明，源自细胞竞争的 WT 细胞的 CDIP 不会影响细胞竞争后其是形成正常组织还是突变克隆过度生长的命运。然而，应该注意的是，CDIP 会加速正常组织形成的速度；这一点仅与我们的预期相符。相比之下，源自自主细胞死亡或细胞竞争的突变细胞的 CDIP 有助于突变细胞的存活。
