Alexander Stephanie, Koehl Gudrun E, Hirschberg Markus, Geissler Edward K, Friedl Peter
Department of Dermatology, Venerology, and Allergology and Rudolf-Virchow Center for Experimental Biomedicine , University of Würzburg, Würzburg, Germany.
Histochem Cell Biol. 2008 Dec;130(6):1147-54. doi: 10.1007/s00418-008-0529-1. Epub 2008 Nov 6.
The metastatic invasion of cancer cells from the primary lesion into the adjacent stroma is a key step in cancer progression, and is associated with poor outcome. The principles of cancer invasion have been experimentally addressed in various in vitro models; however, key steps and mechanisms in vivo remain unclear. Here, we establish a modified skin-fold chamber model for orthotopic implantation, growth and invasion of human HT-1080 fibrosarcoma cells, dynamically reconstructed by epifluorescence and multiphoton microscopy. This strategy allows repeated imaging of tumor growth, tumor-induced angiogenesis and invasion, as either individual cells, or collective strands and cell masses that move along collagen-rich extracellular matrix and coopt host tissue including striated muscle strands and lymph vessels. This modified window model will be suited to address mechanisms of cancer invasion and metastasis, and related experimental therapy.
癌细胞从原发灶向邻近基质的转移侵袭是癌症进展中的关键步骤,且与不良预后相关。癌症侵袭的原理已在各种体外模型中进行了实验研究;然而,体内的关键步骤和机制仍不清楚。在此,我们建立了一种改良的皮肤褶皱腔室模型,用于人HT - 1080纤维肉瘤细胞的原位植入、生长和侵袭,并通过落射荧光显微镜和多光子显微镜进行动态重建。该策略能够对肿瘤生长、肿瘤诱导的血管生成和侵袭进行重复成像,成像对象既可以是单个细胞,也可以是沿着富含胶原蛋白的细胞外基质移动并占据包括横纹肌束和淋巴管在内的宿主组织的集体条索和细胞团块。这种改良的窗口模型将适用于研究癌症侵袭和转移的机制以及相关的实验性治疗。