条件付きで再プログラムされた初代腫瘍細胞の培養と応用

Culture and application of conditionally reprogrammed primary tumor cells.

• Mengjun Zhong
• Liwu Fu

抄録

癌は依然として世界的に人類の生命を脅かす重大な公衆衛生問題であり、基礎・前臨床領域でのさらなる研究が求められている。しかし、臨床トランスレーショナルリサーチの失敗率が高いため、抗がん剤の開発には限界があり、最適ながん研究モデルの開発が急務となっています。がん細胞株、患者由来異種移植（PDX）モデル、オルガノイドの開発は、腫瘍生物学的研究の発展を強力に促進してきたが、その予測値には限界がある。条件付きリプログラミング（CR）は、フィーダー細胞とRho-associated coiled-coil kinase（ROCK）阻害剤を組み合わせた新しいがん研究用細胞培養法であり、初代上皮細胞を迅速かつ連続的に増殖させることが可能である。本総説では、CR モデルの構築方法をまとめ、がん生物学的特徴の研究、治療標的の探索、個別化された薬物スクリーニング、抗がん剤の反応機構の解明、患者由来動物モデルの改良など、最近のがん研究における CR 細胞培養モデルの機能と応用を概観し、最後にこの細胞培養システムの主な限界について詳細に論じています。

Cancer is still a major public-health problem that threatens human life worldwide and further study needs to be carried out in the basic and preclinical areas. Although high-throughput sequencing technology and individualized precise therapy have made breakthroughs over the years, the high failure rate of clinical translational research has limited the innovation of antitumor drugs and triggered the urgent need for optimal cancer-research models. The development of cancerous cell lines, patient-derived xenograft (PDX) models, and organoid has strongly promoted the development of tumor-biology research, but the prediction values are limited. Conditional reprogramming (CR) is a novel cell-culture method for cancer research combining feeder cells with a Rho-associated coiled-coil kinase (ROCK) inhibitor, which enables the rapid and continuous proliferation of primary epithelial cells. In this review, we summarize the methodology to establish CR model and overview recent functions and applications of CR cell-culture models in cancer research with regard to the study of cancer-biology characterization, the exploration of therapeutic targets, individualized drug screening, the illumination of mechanisms about response to antitumor drugs, and the improvement of patient-derived animal models, and finally discuss in detail the major limitations of this cell-culture system.

© The Author(s) 2020. Published by Oxford University Press and Sixth Affiliated Hospital of Sun Yat-sen University.