
ハイドラ属の腫瘍細胞は、長期にわたる垂直伝播の過程で、宿主の触手数を増加させる能力を進化させた。


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While host phenotypic manipulation by parasites is a widespread phenomenon, whether tumors – which can be likened to parasite entities, can also manipulate their hosts is not known. Theory predicts that this should nevertheless be the case, especially when tumors (neoplasms) are transmissible. We explored this hypothesis in a cnidarian Hydra model system, in which spontaneous tumors can occur in the lab, and lineages in which such neoplastic cells are vertically transmitted (through host budding) have been maintained for over 15 years. Remarkably, the hydras with long-term transmissible tumors show an unexpected increase in the number of their tentacles, allowing for the possibility that these neoplastic cells can manipulate the host. By experimentally transplanting healthy as well as neoplastic tissues derived from both recent and long-term transmissible tumors, we found that only the long-term transmissible tumors were able to trigger the growth of additional tentacles. Also, supernumerary tentacles, by permitting higher foraging efficiency for the host, were associated with an increased budding rate, thereby favoring the vertical transmission of tumors. To our knowledge, this is the first evidence that, like true parasites, transmissible tumors can evolve strategies to manipulate the phenotype of their host.

### Competing Interest Statement

The authors have declared no competing interest.

First evidence for the evolution of host manipulation by tumors during the long-term vertical transmission of tumor cells in Hydra oligactis

長期的な腫瘍細胞の垂直伝播中に宿主操作の進化が初めて示された

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腫瘍細胞の分裂、運動、死亡によって固形腫瘍の進化が支配されており、遺伝子変異がこの動態を追跡するためのマーカーとして機能する。高解像度のサンプリングデータを分析した結果、腫瘍は均一な体積成長を示し、表面成長は観察されなかった。


In growing cell populations such as cancer, mutations can serve as markers that allow tracking the past evolution from current samples. The genomic analysis of bulk samples and samples from multiple regions have shed light on the evolutionary forces acting on tumours. However, little is known empirically on the spatio-temporal dynamics of tumour evolution. Here, we leverage published data from resected hepatocellular carcinomas, each with several hundred samples taken in two and three dimensions. Using spatial metrics of evolution, we find that tumour cells grow predominantly uniformly within the tumour volume instead of at the surface. We determine how mutations and cells are dispersed throughout the tumour and how cell death contributes to the overall tumour growth. Our methods shed light on the early evolution of tumours in vivo and can be applied to high-resolution data in the emerging field of spatial biology.

### Competing Interest Statement

The authors have declared no competing interest.

High-density sampling reveals volume growth in human tumours

高密度サンプリングによる人体腫瘍の体積成長の発見