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RANKL Expression Specifically Observed in Vivo Promotes Epithelial Mesenchymal Transition and Tumor Progression

Am J Pathol_178(6)_2845-2856.pdf2.9 MBPDF見る/開く

タイトル: RANKL Expression Specifically Observed in Vivo Promotes Epithelial Mesenchymal Transition and Tumor Progression
著者: Yamada, Tamaki 著作を一覧する
Tsuda, Masumi 著作を一覧する
Takahashi, Tomomi 著作を一覧する
Totsuka, Yasunori 著作を一覧する
Shindoh, Masanobu 著作を一覧する
Ohba, Yusuke 著作を一覧する
発行日: 2011年 6月
出版者: Elsevier
誌名: The American Journal of Pathology
巻: 178
号: 6
開始ページ: 2845
終了ページ: 2856
出版社 DOI: 10.1016/j.ajpath.2011.02.003
抄録: Recent findings have focused attention on the molecular consequences of the microenvironment in tumor progression, but events occurring in cancer cells themselves in response to their ambient conditions remain obscure. Here, we identify receptor activator of nuclear factor κB ligand (RANKL) as a microenvironment-specific factor essential for tumorigenesis in vivo, using head and neck squamous cell carcinoma (HNSCC) as a model. In human HNSCC tissues, RANKL is abundantly expressed, and its expression level correlates with the histological grade of differentiation. RANKL levels are significantly higher in poorly differentiated SCCs than in well or moderately differentiated SCCs. In contrast, all HNSCC cell lines tested displayed extremely low RANKL expression; however, RANKL is efficiently up-regulated when these cell lines are inoculated in the head and neck region of mice. RANKL expression is restored in a microenvironment-specific manner, and cannot be observed when the cells are inoculated in the hindlimbs. Forced expression of RANKL compensates for tumor growth in the hindlimb milieu, promotes epithelial mesenchymal transition, and induces tumor angiogenesis, in a manner independent of vascular endothelial growth factor (VEGF). These results implicate RANKL expression causatively in tumor growth and progression in HNSCC in vivo. RANKL may provide a novel functional marker for biological malignancy and a therapeutic target based on the specific nature of the microenvironment.
資料タイプ: article (author version)
出現コレクション:雑誌発表論文等 (Peer-reviewed Journal Articles, etc)

提供者: 大場 雄介


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