Noël A, De Pauw-Gillet M C, Purnell G, Nusgens B, Lapiere C M, Foidart J M
Laboratory of Cellular Biology, Tour de Pathologie, Sart-Tilman, Liège, Belgium.
Br J Cancer. 1993 Nov;68(5):909-15. doi: 10.1038/bjc.1993.453.
The failure of MCF7 cells to induce the formation of tumours after sub-cutaneous inoculation into athymic nude mice can be obviated by the simultaneous injection of an extract of basement membrane proteins (matrigel). Tumour growth is promoted and the latency period is low (2 to 4 weeks). In the absence of matrigel, the simultaneous inoculation of fibroblasts and MCF7 cells also resulted in the development of tumours, but with a longer latency period (about 2 months). The tumorigenic synergy between matrigel and fibroblasts was evidenced by co-inoculating MCF7 cells MDA-MB 231 cells with fibroblasts and matrigel. This co-inoculation decreased the delay of appearance of the tumours and/or accelerated the tumour growth, depending upon the number of fibroblasts injected. Repeated injections of fibroblasts conditioned medium, at the site of inoculum of tumour cells also enhanced tumour growth, suggesting the involvement of soluble factors secreted by fibroblasts. Histologically, tumours induced by co-inoculation of tumour cells and fibroblasts contained more stromal structures including vimentin-positive cells, fibronectin and interstitial collagens. These data suggest that human tumours may be reconstituted and grown in athymic nude mice using basement membrane components and fibroblasts as inductors.
将MCF7细胞皮下接种到无胸腺裸鼠体内后,若同时注射基底膜蛋白提取物(基质胶),则可避免其无法诱导肿瘤形成的情况。肿瘤生长得到促进,潜伏期缩短(2至4周)。在没有基质胶的情况下,同时接种成纤维细胞和MCF7细胞也会导致肿瘤形成,但潜伏期更长(约2个月)。通过将MCF7细胞、MDA - MB 231细胞与成纤维细胞和基质胶共同接种,证明了基质胶与成纤维细胞之间的致瘤协同作用。这种共同接种减少了肿瘤出现的延迟和/或加速了肿瘤生长,这取决于注射的成纤维细胞数量。在肿瘤细胞接种部位反复注射成纤维细胞条件培养基也能增强肿瘤生长,这表明成纤维细胞分泌的可溶性因子参与其中。从组织学上看,肿瘤细胞与成纤维细胞共同接种诱导形成的肿瘤含有更多的基质结构,包括波形蛋白阳性细胞、纤连蛋白和间质胶原。这些数据表明,使用基底膜成分和成纤维细胞作为诱导剂,可以在无胸腺裸鼠体内重建并培养人类肿瘤。