Huang Chen-Ji, Chou Pei-Kuan, Sher Zong-Yi, Chen You-Rong, Chen Tan-Yueh, Dong Guo-Chung
Institute of Biomedical Engineering and Nanomedicine, National Health Research Institutes, Miaoli 35053, Taiwan.
Graduate Program of Biotechnology in Medicine, National Tsing Hua University, Hsinchu 300044, Taiwan.
Polymers (Basel). 2022 Aug 16;14(16):3340. doi: 10.3390/polym14163340.
Bone tissue attracts cancer cell homing biologically, mechanically, or chemically. It is difficult and time consuming to identify their complex cross-talk using existed methods. In this study, a multi-component bone matrix was fabricated using gelatin, hydroxyapatite (HAp), and epidermal growth factor (EGF) as raw materials to investigate how "acellular" bone matrix affects cancer cell homing in bone. Then, EGF-responsive cancer cells were cultured with the scaffold in a dynamical bioreactor. For different culture periods, the effects of HAp, gelatin, and EGF on the cell adhesion, proliferation, 3D growth, and migration of cancer were evaluated. The results indicated that a small amount of calcium ion released from the scaffolds accelerated cancer MDA-MB-231 adhesion on the surface of inner pores. Moreover, degradable gelatin key caused cancer cell growth on the scaffold surface to turn into a 3D aggregation. Despite this, the formation of cancer spheroids was slow, and required 14 days of dynamic culture. Thankfully, EGF promoted cancer cell adhesion, proliferation, and migration, and cancer spheroids were observed only after 3-day culture. We concluded that the combination of the multiple components in this scaffold allows cancer cells to meet multiple requirements of cancer dynamic progression.
骨组织通过生物学、力学或化学方式吸引癌细胞归巢。使用现有方法识别它们复杂的相互作用既困难又耗时。在本研究中，以明胶、羟基磷灰石（HAp）和表皮生长因子（EGF）为原料制备了一种多组分骨基质，以研究“无细胞”骨基质如何影响癌细胞在骨中的归巢。然后，将对EGF有反应的癌细胞与支架在动态生物反应器中培养。在不同的培养时期，评估了HAp、明胶和EGF对癌细胞黏附、增殖、三维生长和迁移的影响。结果表明，从支架中释放的少量钙离子加速了癌MDA-MB-231在内孔表面的黏附。此外，可降解的明胶关键地使癌细胞在支架表面的生长转变为三维聚集。尽管如此，癌球的形成缓慢，需要14天的动态培养。幸运的是，EGF促进了癌细胞的黏附、增殖和迁移，仅在3天培养后就观察到了癌球。我们得出结论，该支架中多种成分的组合使癌细胞能够满足癌症动态进展的多种需求。
