乳腺肿瘤固体应力调控癌旁脂肪组织细胞核形变及细胞命运转变

癌旁脂肪细胞被证实是促进乳腺肿瘤生长和恶性转移的重要帮凶，深入研究乳腺肿瘤与脂肪组织的相互作用对疾病防治和人口健康具有重大意义。现有的研究表明，肿瘤细胞和脂肪细胞间通过炎症反应和能量代谢相互影响，然后，肿瘤生长所带来的物理力学微环境的急剧变化确被研究者所忽视。本项目提出：乳腺肿瘤通过其生长产生的固体应力极大的改变脂肪细胞细胞核的力学特征，从而影响脂肪细胞的染色质结构，并最终重编程脂肪细胞。为了实现肿瘤生长应力的实时测量和脂肪细胞核形变的实时追踪，申请人将构建肿瘤脂肪共生的三位体外模型，开发活体细胞力学测量技术。本研究重点关注脂肪细胞核的形变，并结合分子生物学手证实肿瘤固体应力对脂肪细胞命运调控起着关键性作用。本项目预期揭示良性、恶性肿瘤对癌旁脂肪细胞不同的固体应力作用形式（张力、收缩力），为深入研究肿瘤多细胞组分力学微环境提供支撑平台，同时促进力学生物学及相关学科的发展和人才培养。

Adipocytes have been shown to be an important driver of the metastasis of mammary tumor. Investigation on the interplays between breast cancer cells and adipocytes benefits our disease prevention and healthcare system. The interaction between adipocytes and cancer cells is currently believed to be a reciprocal metabolic.adaptation. However, the dramatic changes in local mechanical microenvironment during tumor progression has been largely underappreciated. In this project, we propose that the solid stress generated by tumor growth largely alter the mechanical properties of nucleus within the surrounding adipocytes, which will further influence the chromatin structure and reprogram the adipocytes. To study the solid stress generated by mammary tumor and track the deformation of nucleus of adipocytes in real time, we propose to construct a tumor-adipose assembloid, which contains both the tumor part and adipose part in this 3D microtissue. We will further develop live cell mechanical measurements that can capture 4D informations in microtissue. Our study will emphasize on the large deformation of nucleus of adipocytes, and prove the hypothesis that the tumor-generated stresses will significantly change the cell fate of surrounding adipocytes. This project anticipate to reveal different forms of solid stresses that generated by begin and malignant tumors, provide a 3D ex vivo microtissue for the study of mechanobiology in multicomponent tumors, and further benefit for fundamental and translational researches in mechanobiology and cell mechanics.