Contact-activated migration of melanoma B16 and sarcoma XC cells

Contact-activated migration of melanoma B16 and sarcoma XC cells
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DOI:
10.1139/bcb-79-4-425
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发表时间:
2001-08-01
影响因子:
2.9
通讯作者:
Korohoda, W
Korohoda, W
中科院分区:
生物学3区
文献类型:
--
作者:
Madeja, Z;Szymkiewicz, I;Korohoda, W

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在迁移过程中,肿瘤细胞与邻近的肿瘤细胞和正常宿主细胞相互作用,这种相互作用可能会影响它们的运动活性。我们研究了同型碰撞对两种肿瘤细胞系(小鼠黑色素瘤 B16 和大鼠肉瘤 XC)以及未转化的人皮肤成纤维细胞运动活性的影响。研究发现,肿瘤细胞在不与邻近细胞接触的情况下作为单个细胞移动时仅表现出有限的运动活性。在较高密度的培养物(以及更多数量的细胞与细胞接触)下,观察到所研究的肿瘤细胞的运动激活。另一方面,正常人皮肤成纤维细胞表现出典型的密度依赖性运动抑制反应。肿瘤细胞的运动活性不受条件培养基的影响,并且明显依赖于碰撞细胞之间的直接物理接触。肿瘤细胞之间初次接触后约40-50分钟观察到细胞运动的激活。 50 μM 维拉帕米(一种选择性电压门控钙通道抑制剂)和 10 μM 氯化钆(一种机械敏感离子通道的非特异性阻断剂)可抑制接触激活的肿瘤细胞迁移,但百日咳毒素不会抑制肿瘤细胞的接触激活迁移。肿瘤细胞之间的同型碰撞强烈增加其运动活性的观察表明,接触激活的迁移可能在肿瘤侵袭和转移中发挥重要作用。
During migration, tumour cells interact with neighbouring neoplastic and normal host cells, and such interaction may influence their motile activity. We investigated the effect of homotypic collisions on the motile activity of two tumour cell lines, mouse melanoma B16 and rat sarcoma XC, and nontransformed human skin fibroblasts. It was found that the tumour cells show only limited motile activity when moving as single cells without contact with neighbours. At a higher density of the culture (and also at a greater number of cell to cell contacts) the activation of motility of investigated tumour cells was observed. On the other hand, the normal human skin fibroblasts showed a typical reaction of density-dependent inhibition of motility. The motile activity of tumour cells was not affected by conditioned media and was visibly dependent on a direct physical contact among colliding cells. The activation of cell movement was observed about 40-50 min after the initial contact between tumour cells. Contact-activated migration of neoplastic cells was inhibited by 50 muM verapamil (a selective voltage-gated calcium channel inhibitor) and 10 muM gadolinium chloride (a nonspecific blocker of mechanosensitive ion channels) but not by pertussis toxin. The observation that homotypic collisions among tumour cells strongly increase their motile activity suggests that contact-activated migration may play a significant role in tumour invasion and metastasis.