ＭＺＴ（株）ゼブラフィッシュ創薬研究所

新しいヒト癌移植モデルにおける腫瘍血管新生の定量的システムズ薬理学

第86回日本薬理学会年会

Zebrafish-based Quantitative and Systems Pharmacology of Tumor Angiogenesis in Novel Human Cancer XenoTransplantation Model.

Junya Kuroyanagi, Yasuhito Shimada, Noriko Umemoto, Beibei Zhang, Yuhei Nishimura and Toshio Tanaka

Angiogenesis plays an important role in tumor growth and metastasis. Most tumors release angiogenesis regulating factors, and neovasculature occurs when there are predominating positive signaling from regulators of angiogenesis. The use of agents that can inhibit angiogenesis has indicated that anti-angiogenic therapy can be a promising therapeutic approach in clinical cancer treatment. Zebrafish represents a powerful model system in cancer research including tumor angiogenesis. And zebrafish is also exploitable for genome-wide loss-of-function analysis, so we utilized human cancer-engrafted zebrafish searching new drug target against tumor angiogenesis. First, we implanted prostate cancer DU145 cells in zebrafish larvae. After 48 hours from implantation, cancer xenotransplant exhibited tumor angiogenesis. DNA microarray analysis revealed that zebrafish zinc finger, MYND-type containing 8 (zmynd8) was upregulated in tumor angiogenesis. zmynd8 MO suppressed tumor angiogenesis and its mRNA rescue promoted in zebrafish xenotransplant. In summary, we clarified the transcriptome profiles and therapeutic target gene of the tumor angiogenesis using zebrafish.

ＭＺＴ（株）ゼブラフィッシュ創薬研究所

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新しいヒト癌移植モデルにおける腫瘍血管新生の定量的システムズ薬理学