Molecular basis of melanomagenesis based on the failure of pluripotency maintenance of melanocyte stem cells

基于黑素细胞干细胞多能性维持失败的黑色素瘤发生的分子基础

• 批准号: 23591612
• 负责人: MANABE Motomu
• 金额: $ 3.24万
• 依托单位: Akita University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2011
• 资助国家: 日本
• 起止时间: 2011 至 2013
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-23591612/
• 关键词: メラノーマ; スフェロイド; 三酸化ヒ素; サリノマイシン; 幹細胞; PＩ３K; STAT３; 遺伝子改変マウス; ３次元培養法; Stat３

Recurrence after chemotherapy is a major cause of cancer mortality: subsets of tumor cells evade initial chemotherapy or radiotherapy and survive to re-propagate the tumor. To develop a novel therapeutic approach for melanoma, we applied a non-adhesive culture system which developed spheroids mimicking the properties of melanoma in vivo. Subsequently, spheroids involved cells exhibiting clonogenic and slow-cycling properties in addition to chemotherapeutic resistance to doxorubicin. Interestingly, while treatment of spheroids with either salinomycin or As2O3 showed limiting effects, a combinatorial treatment was markedly superior to single treatment with each drug. Thus, melanoma spheroids could be a new platform for studying melanoma biology and are likely to provide a clinically relevant target for the novel chemotherapy.

化疗后复发是癌症死亡的主要原因：肿瘤细胞亚群逃避最初的化疗或放疗并存活以使肿瘤再增殖。为了开发一种新的黑色素瘤治疗方法，我们应用了一种非粘附性培养系统，该系统开发了模拟体内黑色素瘤特性的球状体。随后，球状体涉及除了对阿霉素的化疗抗性之外还表现出克隆形成和慢循环特性的细胞。有趣的是，虽然用盐霉素或As2O3处理球状体显示出有限的作用，但组合处理明显上级用每种药物单独处理。因此，黑色素瘤球体可能是一个新的平台，研究黑色素瘤生物学，并可能提供一个临床相关的目标，为新的化疗。

项目成果

Salinomycin sensitizes melanoma spheroids containing slow-cycling cells to the effects of arsenic trioxide．

Salinomycin 使含有慢周期细胞的黑色素瘤球体对三氧化二砷的作用敏感。

• 发表时间: 2013
• 期刊: Akita J Med
• 作者: 柴垣直孝;島田眞路;NAOTAKA SHIBAGAKI;柴垣直孝;柴垣直孝;柴垣直孝;Ishikawa N,Takahashi M,Noguchi N,Manabe M;Naotaka Shibagaki;Ishikawa N，Takahashi M，Noguchi N，Manabe M．
• 通讯作者: Ishikawa N，Takahashi M，Noguchi N，Manabe M．

Salinomycin sensitizes melanoma spheroids containing slow-cycling cells to the effects of arsenic trioxide

盐霉素使含有慢周期细胞的黑色素瘤球体对三氧化二砷的作用敏感

• 发表时间: 2013
• 期刊: Akita J Med
• 作者: 柴垣直孝;島田眞路;NAOTAKA SHIBAGAKI;柴垣直孝;柴垣直孝;柴垣直孝;Ishikawa N,Takahashi M,Noguchi N,Manabe M
• 通讯作者: Ishikawa N,Takahashi M,Noguchi N,Manabe M