イワモト　タカユキ   Takayuki Iwamoto   岩本　高行    所属   川崎医科大学  医学部 臨床医学　乳腺甲状腺外科学    職種   講師
論文種別	原著
言語種別	英語
査読の有無	査読あり
表題	CSF-1/CSF-1R axis is associated with epithelial/mesenchymal hybrid phenotype in epithelial-like inflammatory breast cancer.
掲載誌名	正式名：Scientific reports 略　 称：Sci Rep ISSNコード：20452322/20452322
掲載区分	国外
巻・号・頁	8(1),pp.9427
著者・共著者	Kazuharu Kai, Takayuki Iwamoto, Dongwei Zhang, Li Shen, Yuko Takahashi, Arvind Rao, Alastair Thompson, Subrata Sen, Naoto T Ueno
担当区分	2nd著者
発行年月	2018/06
概要	Inflammatory breast cancer (IBC) is a rare subtype of breast cancer, accounting for 8-10% of breast cancer-associated deaths in the US. Clinical hallmarks of IBC include tumor emboli in lymphatic vessels and E-cadherin overexpression, which supports a type of metastasis referred to as cell cluster-based metastasis, prevalent in IBC. In contrast, we previously reported epithelial-to-mesenchymal transition (EMT)-based progression of IBC, utilizing in vivo xenografts and in vitro Matrigel culture models. To address these two contradictory concepts of IBC metastasis, we used Matrigel culture to induce EMT in a panel of IBC cells. Results revealed Matrigel culture induced vimentin expression in SUM149 and SUM190 IBC cells at the transcriptional and protein levels while maintaining the expression of E-cadherin, a phenomenon referred to as partial EMT. Transcriptional profiling revealed that expression of colony-stimulating factor 1 (CSF-1) was induced in Matrigel culture. When the receptor tyrosine kinase of CSF-1 (CSF-1R) was inhibited by CSF-1R inhibitor BLZ945, the partial EMT was reversed in a dose-dependent manner, indicating that the CSF-1/CSF-1R axis plays a key role in controlling partial EMT. This observation may help reconcile the two contradictory theories of IBC metastasis, EMT vs cell cluster-based metastasis.
DOI	10.1038/s41598-018-27409-x
PMID	29930294