Hamada J, Nagayasu H, Kawano T, Mizutani T, Nakata D, Hosokawa M, Takeichi N
Division of Cell Biology, Cancer Institute, Hokkaido University School of Medicine, Sapporo, Japan.
Clin Exp Metastasis. 1998 Apr;16(3):291-8. doi: 10.1023/a:1006505211766.
We previously established an experimental model of tumor progression using a weakly malignant rat mammary carcinoma cell line, ER-1. Using this model, we demonstrated that ER-1 cells converted into highly tumorigenic and metastatic cells, ERpP, by s.c. co-inoculation with plastic plates. We here compared in vitro biological properties associated with malignancy of ER-1 cells with those of ERpP cells which were highly malignant when inoculated into syngeneic rats. In vitro growth rate of ERpP cells was higher than that of ER-1 cells under a low nutrient condition. Invasion capacity of ERpP cells to rat lung endothelial cell monolayer or reconstituted basement membrane, Matrigel, was higher than that of ER-1 cells. Migration of ERpP cells toward fibronectin or laminin was also significantly higher than that of ER-1 cells. There was no difference in gelatinolytic or plasminogen activator activity detected in conditioned media between ER-1 and ERpP cells. Furthermore, we found that ER-1 cells communicated better among themselves and with normal fibroblasts through gap junctions compared to ERpP cells. These results suggest that growth advantage in a poor nutrient condition, enhancement of cell motility, and loss or decrease of junctional communication may be associated with tumor progression of ER-1 cells.
我们之前利用一种低恶性的大鼠乳腺癌细胞系ER-1建立了肿瘤进展的实验模型。利用该模型，我们证明通过与塑料平板皮下共接种，ER-1细胞可转化为高致瘤性和转移性的细胞ERpP。在此，我们比较了ER-1细胞与ERpP细胞（接种到同基因大鼠体内时具有高恶性）的体外生物学特性与恶性程度的相关性。在低营养条件下，ERpP细胞的体外生长速率高于ER-1细胞。ERpP细胞对大鼠肺内皮细胞单层或重组基底膜基质胶的侵袭能力高于ER-1细胞。ERpP细胞向纤连蛋白或层粘连蛋白的迁移也显著高于ER-1细胞。在ER-1细胞和ERpP细胞的条件培养基中检测到的明胶酶解或纤溶酶原激活物活性没有差异。此外，我们发现与ERpP细胞相比，ER-1细胞之间以及与正常成纤维细胞之间通过缝隙连接的通讯更好。这些结果表明，在营养条件差时的生长优势、细胞运动性增强以及连接通讯的丧失或减少可能与ER-1细胞的肿瘤进展有关。
