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Different growth and metastatic phenotypes associated with a cell-intrinsic change of Met in metastatic melanoma 酒井, 克也 西内, 巧 今村, 龍 佐藤, 拓輝 松本, 邦夫 マツモト, クニオ 松本 マツモト 邦夫 クニオ Adachi, Eri 10523318 Sakai, Katsuya 20334790 Nishiuchi, Takumi 10311680 Imamura, Ryu 20781173 Sato, Hiroki 90201780 Matsumoto, Kunio © 2017 Impact Journals A dynamic phenotypic change contributes to the metastatic progression and drug resistance in malignant melanoma. Nevertheless, mechanisms for a phenotypic change have remained to be addressed. Here, we show that Met receptor expression changes in a cell-autonomous manner and can distinguish phenotypical differences in growth, as well as in metastatic and drug-resistant characteristics. In metastatic melanoma, the cells are composed of Met-low and Met-high populations. Met-low populations have stem-like gene expression profiles, are resistant to chemotherapeutic agents, and have shown abundant angiogenesis and rapid tumor growth in subcutaneous inoculation. Met-high populations have a differentiated phenotype, are relatively resistant to B-RAF inhibitor, and are highly metastatic to the lungs. Met plays a definitive role in lung metastasis because the lung metastasis of Met-high cells requires Met, and treatment of mice with the Met-containing exosomes from Met-high cells facilitates lung metastasis by Met-low cells. Clonal cell fate analysis showed the hierarchical phenotypical changes from Met-low to Met-high populations. Met-low cells either showed self-renewal or changed into Met-high cells, whereas Met-high cells remained Met-high. Clonal transition from Met-low to Met-high cells accompanied changes in the gene expression profile, in tumor growth, and in metastasis that were similar to those in Met-high cells. These findings indicate that malignant melanoma has the ability to undergo phenotypic change by a cell-intrinsic/autonomous mechanism that can be characterized by Met expression. 金沢大学ナノ生命科学研究所 / 金沢大学がん進展制御研究所 Impact Journals 2016-09-23 2017-10-03 eng journal article VoR https://doi.org/10.24517/00014239 http://hdl.handle.net/2297/46838 https://kanazawa-u.repo.nii.ac.jp/records/14252 10.24517/00014239 10.18632/oncotarget.12221 http://www.impactjournals.com/oncotarget/ Oncotarget 7 43 70779 70793 https://kanazawa-u.repo.nii.ac.jp/record/14252/files/ME-PR-MATSUMOTO-K-70779.pdf application/pdf 7.3 MB 2017-10-03