Li Menglu, Kino-Oka Masahiro
Department of Biotechnology, Graduate School of Engineering, Osaka University, 2-1 Yamadaoka, Suita, Osaka, 565-0871, Japan.
Department of Biotechnology, Graduate School of Engineering, Osaka University, 2-1 Yamadaoka, Suita, Osaka, 565-0871, Japan.
J Biosci Bioeng. 2017 Jun;123(6):748-753. doi: 10.1016/j.jbiosc.2017.01.017. Epub 2017 Mar 11.
Tumor angiogenesis is an important event in tumor malignancy; and the vasculature formed in tumor region is typically dysfunctional. Multiple factors are associated with tumor vessel abnormalities, but the precise mechanism has not been fully understood. In the present study, a tumor-containing cell sheet was prepared by mixing a small population of human embryonal rhabdomyosarcoma (RMS) cells (RDs) with human skeletal muscle myoblasts (HSMMs) to mimic muscle tissue invaded by RMS cells. Sheet fluidity and the extracellular matrix (ECM) meshwork of the tumor-containing cell sheet were found to be elevated and disordered, demonstrating the disruptive effect of tumor cells on sheet structure. When green fluorescent protein expressing human umbilical vein endothelial cells (GFP-HUVECs) were co-cultured with the tumor-containing cell sheet, an endothelial network was formed, but degraded faster as a result of activated migration of endothelial cells in the tumor-containing cell sheet. This study suggested that disorganized tissue structure facilitate tumor angiogenesis by activation of endothelial cell migration.
肿瘤血管生成是肿瘤恶性发展过程中的一个重要事件；肿瘤区域形成的脉管系统通常功能失调。多种因素与肿瘤血管异常相关，但确切机制尚未完全明确。在本研究中，通过将少量人胚胎横纹肌肉瘤（RMS）细胞（RDs）与人类骨骼肌成肌细胞（HSMMs）混合，制备了含肿瘤细胞片，以模拟被RMS细胞侵袭的肌肉组织。发现含肿瘤细胞片的片层流动性和细胞外基质（ECM）网络升高且紊乱，这表明肿瘤细胞对片层结构具有破坏作用。当将表达绿色荧光蛋白的人脐静脉内皮细胞（GFP - HUVECs）与含肿瘤细胞片共培养时，形成了内皮网络，但由于含肿瘤细胞片中内皮细胞的活化迁移，该网络降解更快。本研究表明，组织结构紊乱通过激活内皮细胞迁移促进肿瘤血管生成。
