title: Disruption of myoblast alignment by highly motile rhabdomyosarcoma cell in tissue structure.
abstract: Rhabdomyosarcoma (RMS) is a highly malignant tumor type of skeletal muscle origin, hallmarked by local invasion. Interaction between invasive tumor cells and normal cells plays a major role in tumor invasion and metastasis. Culturing tumor cells in a three-dimensional (3D) model can translate tumor malignancy relevant cell-cell interaction. To mimic tumor heterogeneity in vitro, a co-culture system consisting of a malignant embryonal rhabdomyosarcoma (ERMS) cell line RD and a normal human skeletal muscle myoblast (HSMM) cell line was established by cell sheet technology. Various ratios of RDs to HSMMs were employed to understand the quantitative effect on intercellular interactions. Disruption of sheet structure was observed in heterogeneous cell sheets having a low ratio of RDs to HSMMs, whereas homogeneous HSMM or RD sheets maintained intact structure. Deeper exploration of dynamic tumor cell behavior inside HSMM sheets revealed that HSMM cell alignment was disrupted by highly motile RDs. This study demonstrated that RMS cells are capable of compromising their surrounding environment through induced decay of HSMMs alignment in a cell-based 3D system. This suggests that muscle disruption might be a major consequence of RMS cell invasion into muscles, which could be a promising target to preventing tumor invasion.
authors: Department of Biotechnology, Graduate School of Engineering, Osaka University, 2-1 Yamadaoka, Suita, Osaka 565-0871, Japan.
authors: Menglu
authors: M
authors: Li
authors: Department of Biotechnology, Graduate School of Engineering, Osaka University, 2-1 Yamadaoka, Suita, Osaka 565-0871, Japan.
authors: Eiji
authors: E
authors: Nagamori
authors: Department of Biotechnology, Graduate School of Engineering, Osaka University, 2-1 Yamadaoka, Suita, Osaka 565-0871, Japan. Electronic address: kino-oka@bio.eng.osaka-u.ac.jp.
authors: Masahiro
authors: M
authors: Kino-Oka
mesh_terms: D002448:Cell Adhesion; D002450:Cell Communication; D018929:Cell Culture Techniques / Q000379:methods; D002460:Cell Line; D045744:Cell Line, Tumor; D002465:Cell Movement; D002478:Cells, Cultured; D018920:Coculture Techniques / Q000379:methods; D006801:Humans; D007365:Intercellular Junctions / Q000473:pathology / Q000502:physiology; D018482:Muscle, Skeletal / Q000166:cytology* / Q000502:physiology*; D032448:Myoblasts, Skeletal / Q000166:cytology* / Q000502:physiology*; D009361:Neoplasm Invasiveness; D012208:Rhabdomyosarcoma / Q000473:pathology*; D057705:Transendothelial and Transepithelial Migration
keywords: 3D culture; Cell–cell interaction; Myoblast alignment; Rhabdomyosarcoma; Time-lapse movie; Tumor microenvironment