Ohba N, Maeda M, Sakamoto H, Kiyama H, Ishii M, Muraoka M, Kaneda K
Department of Anatomy, Graduate School of Medicine, Osaka City University, Osaka, Japan.
J Submicrosc Cytol Pathol. 2002 Oct;34(4):367-76.
This study was aimed to demonstrate the regeneration of skeletal muscle fibers in the stroma reaction during tumor invasion, using the rat model of tongue carcinoma. By oral administration of 4-nitroquinoline N-oxide, squamous cell carcinoma (SCC) appeared in the epithelium, and deeply invaded the muscular layer, inducing the stroma reaction around the tumor. Regenerating muscle fibers, characterized by the immature profiles of sparse myofibrils, centrally disposed multi-nuclei, and abundant mitochondria, were extended from the surrounding normal muscles into the stroma. By immunohistochemistry, some of them expressed BF-45, a marker for an early stage of myodifferentiation, similar to the regenerating muscle fibers in the bupivacaine hydrochloride-induced injury. They were closely associated with the stromal components such as ED-1-positive macrophages, alpha-smooth muscle actin-positive myofibroblasts, and factor VIII-related antigen-positive vascular endothelial cells, suggesting the roles of their interactions in muscle regeneration. Immature muscle fibers were usually devoid of acetylcholinesterase-positive endplates on them, but some were reinnervated by the terminal axons. The present results indicate that skeletal muscle regeneration is induced in association with the stroma reaction during SCC invasion in the tongue.
本研究旨在利用大鼠舌癌模型,证明肿瘤侵袭过程中基质反应时骨骼肌纤维的再生情况。通过口服4-硝基喹啉N-氧化物,上皮细胞出现鳞状细胞癌(SCC),并深深侵入肌层,诱导肿瘤周围的基质反应。再生的肌纤维从周围正常肌肉延伸至基质,其特征为肌原纤维稀疏、中央多核且线粒体丰富的不成熟形态。通过免疫组织化学方法,其中一些肌纤维表达BF-45,这是肌分化早期的标志物,类似于盐酸布比卡因诱导损伤中的再生肌纤维。它们与基质成分如ED-1阳性巨噬细胞、α-平滑肌肌动蛋白阳性肌成纤维细胞以及因子VIII相关抗原阳性血管内皮细胞密切相关,提示它们之间的相互作用在肌肉再生中发挥作用。不成熟的肌纤维通常没有乙酰胆碱酯酶阳性终板,但有些会被轴突终末重新支配。目前的结果表明,在舌部SCC侵袭过程中,骨骼肌再生与基质反应相关。