Department of Ecology, School of Biology/Chemistry, Osnabrück University, Osnabrück, Germany.
Santa Fe Institute, Santa Fe, NM, 87501, USA.
Sci Rep. 2020 Jan 20;10(1):674. doi: 10.1038/s41598-020-57494-w.
Cooperation between cells in multicellular organisms is preserved by an active regulation of growth through the control of cell division. Molecular signals used by cells for tissue growth are usually present during developmental stages, angiogenesis, wound healing and other processes. In this context, the use of molecular signals triggering cell division is a puzzle, because any molecule inducing and aiding growth can be exploited by a cancer cell, disrupting cellular cooperation. A significant difference is that normal cells in a multicellular organism have evolved in competition between high-level organisms to be altruistic, being able to send signals even if it is to their detriment. Conversely, cancer cells evolve their abuse over the cancer's lifespan by out-competing their neighbours. A successful mutation leading to cancer must evolve to be adaptive, enabling a cancer cell to send a signal that results in higher chances to be selected. Using a mathematical model of such molecular signalling mechanism, this paper argues that a signal mechanism would be effective against abuse by cancer if it affects the cell that generates the signal as well as neighbouring cells that would receive a benefit without any cost, resulting in a selective disadvantage for a cancer signalling cell. We find that such molecular signalling mechanisms normally operate in cells as exemplified by growth factors. In scenarios of global and local competition between cells, we calculate how this process affects the fixation probability of a mutant cell generating such a signal, and find that this process can play a key role in limiting the emergence of cancer.
细胞间的合作是通过控制细胞分裂来积极调节生长来维持的。细胞用于组织生长的分子信号通常存在于发育阶段、血管生成、伤口愈合和其他过程中。在这种情况下，使用触发细胞分裂的分子信号是一个难题，因为任何诱导和促进生长的分子都可能被癌细胞利用，破坏细胞间的合作。一个显著的区别是，多细胞生物中的正常细胞在与高等生物的竞争中进化为利他主义，即使这对它们自己不利，它们也能够发送信号。相反，癌细胞通过与邻居竞争而在癌症的生命周期中进化为滥用。导致癌症的成功突变必须进化为适应性，使癌细胞能够发出信号，从而增加被选择的机会。本文使用这种分子信号机制的数学模型进行论证，如果信号机制不仅影响产生信号的细胞，而且还影响接收信号而无需任何代价的邻近细胞，从而导致癌细胞信号发送细胞的选择劣势，那么这种信号机制将有效地防止癌症的滥用。我们发现，这种分子信号机制通常在细胞中运作，例如生长因子。在细胞之间的全球和局部竞争场景中，我们计算了这个过程如何影响产生这种信号的突变细胞的固定概率，并发现这个过程可以在限制癌症的出现方面发挥关键作用。
