Young M R, Young M E, Wepsic H T
Cancer Res. 1987 Jul 15;47(14):3679-83.
The role of prostaglandin E2 (PGE2) in directly stimulating metastatic spread by Lewis lung carcinoma (LLC) cells was examined with the use of an in vitro migration model for tumor dissemination. The extent to which cloned metastatic and nonmetastatic LLC cells migrated out of glass capillary tubes in vitro reflected their capacity to form pulmonary metastases in vivo. The addition of PGE2 to metastatic LLC cells further stimulated their migration. Other cyclooxygenase products, besides PGE2, did not stimulate the migration of metastatic LLC cells. Nonmetastatic LLC cells did not migrate out of capillary tubes, even in the presence of exogenous PGE2. The amount of PGE2 secreted by cloned LLC cells was quantitated by a radioimmunoassay. Nonmetastatic LLC cells secreted more PGE2 than did the metastatic LLC cells. When the nonmetastatic LLC cells were either mixed with or placed adjacent to cloned metastatic LLC cells, the migration by the metastatic LLC cells was stimulated. The migration-stimulatory capacity of the nonmetastatic LLC cells was minimized in the presence of indomethacin, a prostaglandin synthesis inhibitor. Studies were conducted to relate these in vitro results to tumor metastasis in vivo. Injection of a mixture of metastatic and nonmetastatic LLC cells into mice s.c. resulted in a greater number of lung metastases than did injection of metastatic cells alone. This increase in metastasis formation was prevented by indomethacin. Formation of pulmonary metastases was also augmented when irradiated nonmetastatic LLC cells were injected into metastatic LLC-bearing mice. The results of our studies suggest that nonmetastatic LLC cells, by producing PGE2, can augment in vitro migration and in vivo dissemination of metastatic LLC cells. Thus, the response of tumor cells to PGE2, rather than simply their production of PGE2, appears to be important in regulating tumor dissemination.
利用肿瘤播散的体外迁移模型，研究了前列腺素E2（PGE2）在直接刺激Lewis肺癌（LLC）细胞发生转移扩散中的作用。克隆的转移性和非转移性LLC细胞在体外从玻璃毛细管中迁移出来的程度反映了它们在体内形成肺转移的能力。向转移性LLC细胞中添加PGE2进一步刺激了它们的迁移。除PGE2外，其他环氧化酶产物均未刺激转移性LLC细胞的迁移。即使存在外源性PGE2，非转移性LLC细胞也不会从毛细管中迁移出来。通过放射免疫测定法定量克隆的LLC细胞分泌的PGE2量。非转移性LLC细胞分泌的PGE2比转移性LLC细胞多。当非转移性LLC细胞与克隆的转移性LLC细胞混合或相邻放置时，转移性LLC细胞的迁移受到刺激。在前列腺素合成抑制剂吲哚美辛存在的情况下，非转移性LLC细胞的迁移刺激能力降至最低。开展研究以将这些体外结果与体内肿瘤转移相关联。将转移性和非转移性LLC细胞的混合物注射到小鼠皮下，比单独注射转移性细胞导致更多的肺转移。吲哚美辛可阻止转移形成的这种增加。当将经辐照的非转移性LLC细胞注射到携带转移性LLC的小鼠中时，肺转移的形成也会增加。我们的研究结果表明，非转移性LLC细胞通过产生PGE2，可以增强转移性LLC细胞的体外迁移和体内播散。因此，肿瘤细胞对PGE2的反应，而不仅仅是它们产生PGE2，似乎在调节肿瘤播散中很重要。
