Glucose Transporter 1-Mediated Transcytosis of Glucosamine-Labeled Liposomal Ceramide Targets Hypoxia Niches and Cancer Stem Cells to Enhance Therapeutic Efficacy

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題名:	Glucose Transporter 1-Mediated Transcytosis of Glucosamine-Labeled Liposomal Ceramide Targets Hypoxia Niches and Cancer Stem Cells to Enhance Therapeutic Efficacy
作者:	沈耀安 Yu, Lu-Yi;Shueng, Pei-Wei;Chiu, Hsin-Cheng;Yu-Wei, Yen 1;Tzu-Yu, Kuo 1;Chieh-Ru, Li 1;Ming-Wei, Liu 1;Chia-Hsin, Ho 1;Tzu-Hao, Ho 1;Bo-Wei, Wang 1;Cheng-En, Li 1;Ming-Hung, Chen 1;Yao-An, Shen 5;Lo, Chun-Liang
貢獻者:	醫學系病理學科
關鍵詞:	cancer stem cells;ceramide;glucose transporter;hypoxia-targeting;transcytosis.
日期:	2023-07
上傳時間:	2024-12-04 14:04:48 (UTC+8)
摘要:	Tumour hypoxia plays an important role in modulating tumorigenesis; angiogenesis; invasion; immunosuppression; resistance to treatment; and even maintenance of the stemness of cancer stem cells (CSCs). Moreover; the targeting and treatment of hypoxic cancer cells and CSCs to reduce the influence of tumor hypoxia on cancer therapy remains an imperative clinical problem that needs to be addressed. Since cancer cells upregulate the expression of glucose transporter 1 (GLUT1) through the Warburg effect; we considered the possibility of GLUT1-mediated transcytosis in cancer cells and developed a tumor hypoxia-targeting nanomedicine. Our experimental results indicate that glucosamine-labeled liposomal ceramide can be efficiently transported between cancer cells by GLUT1 transporters and substantially accumulated in the hypoxic area in in vitro CSC spheroids and in vivo tumor xenografts. We also verified the effects of exogenous ceramide on tumor hypoxia; including important bioactivities such as upregulation of p53 and retinoblastoma protein (RB); downregulation of hypoxia-inducible factor-1 alpha (HIF-1α) expression; disruption of the OCT4-SOX2 network of stemness; and inhibition of CD47 and PD-L1 expression. To achieve an ideal therapeutic outcome; we combined treatment of glucosamine-labeled liposomal ceramide with paclitaxel and carboplatin; and we found an excellent synergistic effect; with tumor clearance being noted in three-fourths of the mice. Overall; our findings provide a potential therapeutic strategy for the treatment of cancer.
關聯:	ACS nano; 17(14); 13158–13175
描述:	【112-2 升等】臺北醫學大學教師升等專門著作職別：專任送審等級：副教授著作送審
附註:	代表著作名稱：《Glucose Transporter 1-Mediated Transcytosis of Glucosamine-Labeled Liposomal Ceramide Targets Hypoxia Niches and Cancer Stem Cells to Enhance Therapeutic Efficacy》
資料類型:	article
顯示於類別:	[教師升等送審著作] 112 [病理學科] 期刊論文

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