Laboratory for Histogenetic Dynamics, Graduate School of Life Sciences, Tohoku University, Sendai, 980-8578, Japan.
Frontier Research Institute for Interdisciplinary Sciences, Tohoku University, Sendai, 980-8578, Japan.
Sci Rep. 2023 Jul 30;13(1):12334. doi: 10.1038/s41598-023-38489-9.
Patient-derived xenograft (PDX) is an emerging tool established in immunodeficient vertebrate models to assess individualized treatments for cancer patients. Current xenograft models are deficient in adaptive immune systems. However, the precise role of the innate immunity in the xenograft models is unknown. With conserved signaling pathways and established genetic tools, Drosophila has contributed to the understanding of the mechanism of tumor growth as well as tumor-host interactions for decades, making it a promising candidate model for studying whether or not the hosts' innate immunity can accommodate transplanted human tumor cells. Here we show initial observations that assess the behavior and impact of several human tumor cell lines when transplanted into Drosophila. We found that some injected cell lines persisted for a longer duration and reduced hosts' lifespan. In particular, the human lung cancer cell line A549 were observed adjacent to the fly host tissues. We examined two factors that affect the survivability of cancer cells: (1) the optimal temperature of each cell line and (2) the innate immunity of Drosophila hosts. Especially, transplanted human tumor cells survived longer in immunodeficient flies, suggesting that the host innate immune system impedes the growth of xenografted cells. Our attempts for xenografting fly models thus provide necessary steps to overcome for establishing PDX cancer models using invertebrates.
患者来源异种移植（PDX）是一种在免疫缺陷脊椎动物模型中建立的新兴工具，用于评估癌症患者的个体化治疗。目前的异种移植模型缺乏适应性免疫系统。然而，先天免疫系统在异种移植模型中的精确作用尚不清楚。由于保守的信号通路和已建立的遗传工具，果蝇几十年来为理解肿瘤生长的机制以及肿瘤-宿主相互作用做出了贡献，使其成为研究宿主先天免疫是否能够容纳移植的人类肿瘤细胞的有前途的候选模型。在这里，我们展示了初步观察结果，评估了几种人类肿瘤细胞系移植到果蝇中的行为和影响。我们发现，一些注射的细胞系持续时间更长，缩短了宿主的寿命。特别是，观察到人类肺癌细胞系 A549 与果蝇宿主组织相邻。我们研究了影响癌细胞存活率的两个因素：（1）每个细胞系的最佳温度和（2）果蝇宿主的先天免疫系统。特别是，在免疫缺陷的果蝇中，移植的人类肿瘤细胞存活时间更长，这表明宿主先天免疫系统阻碍了异种移植细胞的生长。我们对异种移植果蝇模型的尝试因此为使用无脊椎动物建立 PDX 癌症模型提供了必要的步骤。
