Institute of Life Sciences, Vasile Goldiş Western University of Arad, Arad, Romania.
Institute of Biophysics, Biological Research Centre, Hungarian Academy of Sciences, Szeged, Hungary.
J Cell Mol Med. 2019 Apr;23(4):2619-2631. doi: 10.1111/jcmm.14156. Epub 2019 Feb 2.
Breast cancer and melanoma are among the most frequent cancer types leading to brain metastases. Despite the unquestionable clinical significance, important aspects of the development of secondary tumours of the central nervous system are largely uncharacterized, including extravasation of metastatic cells through the blood-brain barrier. By using transmission electron microscopy, here we followed interactions of cancer cells and brain endothelial cells during the adhesion, intercalation/incorporation and transendothelial migration steps. We observed that brain endothelial cells were actively involved in the initial phases of the extravasation by extending filopodia-like membrane protrusions towards the tumour cells. Melanoma cells tended to intercalate between endothelial cells and to transmigrate by utilizing the paracellular route. On the other hand, breast cancer cells were frequently incorporated into the endothelium and were able to migrate through the transcellular way from the apical to the basolateral side of brain endothelial cells. When co-culturing melanoma cells with cerebral endothelial cells, we observed N-cadherin enrichment at melanoma-melanoma and melanoma-endothelial cell borders. However, for breast cancer cells N-cadherin proved to be dispensable for the transendothelial migration both in vitro and in vivo. Our results indicate that breast cancer cells are more effective in the transcellular type of migration than melanoma cells.
乳腺癌和黑色素瘤是导致脑转移的最常见癌症类型之一。尽管具有不可置疑的临床意义，但中枢神经系统继发性肿瘤的许多重要方面尚未得到充分描述，包括转移细胞通过血脑屏障的渗出。我们使用透射电子显微镜，在此观察到癌细胞和脑内皮细胞在黏附、插入/整合和穿内皮迁移步骤中的相互作用。我们观察到，脑内皮细胞通过向肿瘤细胞伸出类似丝状伪足的膜突起，积极参与渗出的初始阶段。黑色素瘤细胞往往在内皮细胞之间插入，并通过细胞旁途径进行迁移。另一方面，乳腺癌细胞经常被整合到内皮细胞中，并能够通过从脑内皮细胞的顶侧向基底侧的细胞内途径迁移。当将黑色素瘤细胞与脑内皮细胞共培养时，我们观察到黑色素瘤-黑色素瘤和黑色素瘤-内皮细胞边界处 N-钙粘蛋白的富集。然而，对于乳腺癌细胞，N-钙粘蛋白在体外和体内的穿内皮迁移中被证明是可有可无的。我们的结果表明，乳腺癌细胞在细胞内型迁移中的效率高于黑色素瘤细胞。
