A fludic material-based dynamic cell culture platform as an ex vivo disease model of breast cancer metastasis

基于流体材料的动态细胞培养平台作为乳腺癌转移的离体疾病模型

• 批准号: 21J10260
• 负责人: NAJMINA MAZAYA
• 金额: $ 0.96万
• 依托单位: University of Tsukuba
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for JSPS Fellows
• 财政年份: 2021
• 资助国家: 日本
• 起止时间: 2021-04-28 至 2023-03-31
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-21J10260/
• 关键词: stress relaxation time; viscosity; breast cancer cell; molecular weight; low molecular weight; cell cycle arrest; reactive oxygen species; Senescence; Surface Fluidity; Cancer Stemness; Quiescence

Through culturing the breast cancer cell line (MCF-7) on a viscous-dominant viscoelastic polymer substrate, it was demonstrated that stress relaxation time of the polymeric substrate is the dominant parameter that regulates the cell cycle arrest of non-invasive breast cancer cells. This research firstly reported that breast cancer cells can sense the material relaxation time at the range of milliseconds (80-290 ms). The viscous-dominant polymeric material induced the cellular senescence of breast cancer cellsthrough the generation of reactive oxygen species. Moreover, I was able to demonstrate that we can directly tune the the cellular fate of breast cancer cells by manipulating the molecular properties of the polymer (molecular weight distribution and molecular weight). The intracellular function and growth state of MCF7 cells are able to be manipulated by changing the molecular weight distribution (MWD) of a copolymer. Increasing the MWD (MWD > 1.5) promoted cell populations to form multicellular aggregates due to the decreasing bulk stress relaxation time of the substrate. The presence of low molecular weight polymer which results in MWD > 1.5 can switch the proliferative fate of breast cancer cells (MCF7) into cell cycle arrest fate accompanied by the generation of reactive oxygen species. Through those findings, I was also able to propose a new non-invasive method to distinguish the senescent cells from dormant cells and cells in normal-growth state based on the total protein content of cells through a phase difference by quantitative phase microscopy technique.

通过在粘弹性聚合物基质上培养乳腺癌细胞系（MCF-7），证明了聚合物基质的应力松弛时间是调节非侵袭性乳腺癌细胞周期阻滞的主要参数。本研究首次报道了乳腺癌细胞可以感知到物质松弛时间在毫秒（80-290毫秒）的范围内。黏性优势高分子材料通过产生活性氧诱导乳腺癌细胞衰老。此外，我能够证明我们可以通过操纵聚合物的分子特性（分子量分布和分子量）直接调整乳腺癌细胞的细胞命运。通过改变共聚物的分子量分布（MWD），可以控制MCF7细胞的胞内功能和生长状态。增加MWD (MWD > 1.5)，由于底物的体积应力松弛时间减少，促进细胞群体形成多细胞聚集体。低分子量聚合物的存在导致MWD > 1.5，可以将乳腺癌细胞（MCF7）的增殖命运转变为伴随活性氧产生的细胞周期阻滞命运。通过这些发现，我也能够提出一种新的无创方法，通过定量相显微镜技术，通过细胞的总蛋白含量，通过相位差来区分衰老细胞与休眠细胞和正常生长状态的细胞。

项目成果

Material Fluidity Promotes the Senescence of BReast Cancer Cells in a Fluidity-dependent Manner

材料流动性以流动性依赖性方式促进乳腺癌细胞衰老

• 发表时间: 2021
• 作者: Yoneda Saki;Maruno Takahiro;Mori Asuka;Hioki Ayana;Nishiumi Haruka;Okada Rio;Murakami Makoto;Zekun Wang;Fukuhara Ayano;Itagaki Nozomi;Harauchi Yosuke;Adachi Satoru;Okuyama Kumi;Sawaguchi Taichi;Torisu Tetsuo;Uchiyama Susumu;村山雄紀;Mazaya Najmina;伊藤聡・斎藤英喜編;Saki Yoneda;村山雄紀;Akihito Mori and Yuya Murakami;Mazaya Najmina;栗田英彦編;Mazaya Najmina;村山雄紀;米田早紀;Akihito Mori;村山雄紀;森 祥仁;Mazaya Najmina;森祥仁;Mazaya Najmina
• 通讯作者: Mazaya Najmina

Material fluidity-induced inactivation of breast cancer cells through aggregation: An In Depth Study

材料流动性通过聚集诱导乳腺癌细胞失活：一项深入研究

• 发表时间: 2022
• 作者: Yoneda Saki;Maruno Takahiro;Mori Asuka;Hioki Ayana;Nishiumi Haruka;Okada Rio;Murakami Makoto;Zekun Wang;Fukuhara Ayano;Itagaki Nozomi;Harauchi Yosuke;Adachi Satoru;Okuyama Kumi;Sawaguchi Taichi;Torisu Tetsuo;Uchiyama Susumu;村山雄紀;Mazaya Najmina
• 通讯作者: Mazaya Najmina

The Interplay Between Substrate Fluidity and Cell Adhesion Protein on Triggering the Senescence Fate of Breast Cancer Cells

底物流动性和细胞粘附蛋白之间的相互作用触发乳腺癌细胞的衰老命运

• 发表时间: 2021
• 作者: Satoko Tokunaga;Ed Potten;Yuta Nishikawa;and Yuki Sugiyama;Mazaya Najmina
• 通讯作者: Mazaya Najmina

The Bulk Stress Relaxationof a Viscoelastic Liquid Matrix Manipulates the Depth of the Cell Cycle Arrest of Breast Cancer Cells

粘弹性液体基质的体积应力松弛控制乳腺癌细胞细胞周期停滞的深度

• 发表时间: 2022
• 作者: Najmina Mazaya;Ebara Mitsuhiro;Ohmura Takahito;Uto Koichiro;山下久夫・斎藤英喜編;井口大幹;村山雄紀;Mazaya Najmina
• 通讯作者: Mazaya Najmina

Determining the trigger of breast cancer inactivation state on the fluidic substrate: Bulk vs near-surface mobility?

确定流体基质上乳腺癌失活状态的触发因素：本体迁移率与近表面迁移率？

• 发表时间: 2021
• 作者: Yoneda Saki;Maruno Takahiro;Mori Asuka;Hioki Ayana;Nishiumi Haruka;Okada Rio;Murakami Makoto;Zekun Wang;Fukuhara Ayano;Itagaki Nozomi;Harauchi Yosuke;Adachi Satoru;Okuyama Kumi;Sawaguchi Taichi;Torisu Tetsuo;Uchiyama Susumu;村山雄紀;Mazaya Najmina;伊藤聡・斎藤英喜編;Saki Yoneda;村山雄紀;Akihito Mori and Yuya Murakami;Mazaya Najmina;栗田英彦編;Mazaya Najmina;村山雄紀;米田早紀;Akihito Mori;村山雄紀;森 祥仁;Mazaya Najmina
• 通讯作者: Mazaya Najmina