本研究では, 膵癌細胞が発現し得る細胞小器官, primary ciliaに注目した。我々はprimary ciliaを有する膵癌が悪性度が高いことを示したが, そのメカニズムは不明であった。我々はRNAi法を用いて, primary cilia形成に必要な分子(IFT88, KIF3A)がin vitroでのコロニー形成能やin vivoでの腫瘍形成能に寄与することを見出した。本研究結果は, 極性の乱れは少ないがリンパ節転移は多いというprimary cilia発現膵癌の特徴をよく反映したものであった。本研究成果は高悪性度の膵癌のメカニズム解明や新規治療ターゲット開拓への寄与が期待される。
The study focuses on primary cilia, which is one of the cellular organelles and can be formed in pancreatic cancer cells. Pancreatic cancer with primary cilia is recently recognized as a high-grade one, however, the mechanism is unclear. In this study, we clarify that IFT88 and KIF3A, which are necessary to form primary cilia, are related to colony formation in vitro and tumor formation in vivo. These results reflect the character of pancreatic cancer with primary cilia ; relatively well-differentiated morphology and the high ability of lymph node metastases. Our results are expected to contribute to analysis of the aggressiveness and the exploitation of novel therapeutic targets for pancreatic cancer.
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