Patient-derived Xenografts from Colorectal Carcinoma: A Temporal and Hierarchical Study of Murine Stromal Cell Replacement
Patient-derived Xenografts from Colorectal Carcinoma: A Temporal and Hierarchical Study of Murine Stromal Cell Replacement
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DOI：
10.21873/anticanres.11707
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发表时间：
2017-07-01
影响因子：
2
通讯作者：
Hellmich, Mark R.
中科院分区：
文献类型：
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作者：
Chao, Celia;Widen, Steve G.;Hellmich, Mark R.
背景/目的：人结直肠癌（CRC）的患者来源的异种移植（PDX）是研究肿瘤对治疗剂的反应的优选实验模型。逐渐地，人基质细胞被小鼠基质细胞取代;然而，在人CRC异种移植物中用鼠基质细胞取代人基质细胞的确切时间尚未完全阐明。我们假设，orthopathic小鼠转录功能的替代损失，由于更换人类基质基因。材料和方法：将人CRC重复植入无胸腺裸鼠中，并随时间随访。使用下一代测序，我们确定了人类基质细胞替代的时间动力学与orthopathic鼠成绩单。结果如下：CRC细胞诱导的正常、静止的鼠基质细胞重组为支持人CRC生长的促肿瘤表型发生在初始植入时。结论：小鼠细胞替代具有时间和大小依赖性。
Background/Aim: Patient-derived xenografting (PDX) of human colorectal cancer (CRC) is the preferred experimental model to study tumor response to therapeutic agents. Gradually, human stromal cells are replaced by mouse stromal cells; however, the exact timing of the replacement of human with murine stromal cells in human CRC xenograft has not been fully elucidated. We hypothesize that orthologous murine transcripts functionally substitutes for the loss due to replacement of human stromal genes. Materials and Methods: Human CRC were implanted in athymic nude mice in replicates and followed-up over time. Using next-generation sequencing, we determined the temporal kinetics of human stromal cell replacement with the orthologous murine transcripts. Results: CRC cell-induced re-organization of the normal, quiescent murine stromal cells into a protumorigenic phenotype supporting human CRC growth occurs at initial implantation. Conclusion: Murine cell replacement occurs in a time-and size-dependent manner.