Abstract：
Primary cancer modulates the bone microenvironment to sow the seeds of dormancy and metastasis in tumor cells, leading to multiple organ metastasis and death. In this study, 3D printing and bone-on-a-chip (BOC) are combined to develop a BOC platform that mimics the pre-metastatic niches (PMNs) and facilitates elucidation of the interactions between bone-resident cells and metastatic tumor cells under the influence of primary cancer. Photocrosslinkable gelatin methacrylate (GelMA) is used as a 3D culturing hydrogel to encapsulate cells, and circulate tumor culture medium (CM) adjacent to the hydrogel to verify the critical role of mesenchymal stem cells (MSCs) and osteoclasts (RAW264.7s). Three niches: the dormancy niche, the perivascular niche, and the \"vicious cycle\" niche, are devised to recapitulate bone metastasis in one chip with high cell viability and excellent nutrient exchange. With respect to tumor dormancy and reactivation, the invadopodia formation of A549 lung cancer cells in communication with MSCs and RAW264.7 via the cortactin pathway is researched. As a proof of concept, the functionality and practicality of the platform are demonstrated by analyzing the invadopodia formation and the influence of various cells, and the establishment of the dynamic niches paves the way to understanding PMN formation and related drug discovery.
摘要：
原发癌调节骨微环境，在肿瘤细胞中播下休眠和转移的种子，导致多器官转移和死亡。在这项研究中,3D打印和芯片上骨骼（BOC）相结合，开发了一种BOC平台，该平台可以模拟转移前的壁ni（PMN），并有助于阐明在原发癌的影响下，骨骼驻留细胞与转移性肿瘤细胞之间的相互作用。光可交联明胶甲基丙烯酸酯（GelMA）用作3D培养水凝胶来封装细胞，与水凝胶相邻的肿瘤培养基（CM）循环，以验证间充质干细胞（MSCs）和破骨细胞（RAW264.7s）的关键作用。三个生态位：休眠生态位，血管周围的小生境,和“恶性循环”利基，旨在在具有高细胞活力和出色营养交换的一个芯片中概括骨转移。关于肿瘤休眠和再激活，研究了通过cortactin途径与MSCs和RAW264.7通讯的A549肺癌细胞的invadopodia形成。作为概念的证明，通过分析invadopodia的形成和各种细胞的影响，证明了平台的功能性和实用性，动态生态位的建立为理解PMN的形成和相关药物的发现铺平了道路。
