Wang Xiaowei, Ferreira Alexander M, Shao Qing, Laird Dale W, Sandig Martin
Department of Anatomy and Cell Biology, University of Western Ontario, London, Ontario, Canada.
Prostate. 2005 Apr 1;63(1):65-80. doi: 10.1002/pros.20168.
beta3 integrins play a role in metastatic progression of prostate cancer by mediating adhesion of cancer cells to endothelium and migration through extracellular matrix (ECM). However, the role of beta3 integrins during transendothelial migration (TEM) of prostate tumor cells is poorly understood. We examined the role of beta3 integrins in TEM of PC3 human prostate cancer cells through a monolayer of human lung microvascular endothelial cells (HLMVECs).
PC3 cells were challenged with beta3 integrin antibodies or antisense nucleotides and their efficiency to migrate through monolayers of endothelial cells (ECs) was assessed using confocal microscopy.
beta3 integrins in PC3 cells are not localized in focal contacts and their blockade significantly inhibited TEM by over 50% preferentially during late stages of migration. Formation of PC3 cell pseudopodia on matrigel was significantly reduced by beta3 integrin antisense oligonucleotides.
beta3 integrins play important roles during TEM of PC3 cells while interacting with the matrix underneath the endothelium. These interactions are independent of the ability to cluster beta3 integrins into focal adhesions.
β3整合素通过介导癌细胞与内皮细胞的黏附以及通过细胞外基质（ECM）迁移，在前列腺癌的转移进展中发挥作用。然而，β3整合素在前列腺肿瘤细胞跨内皮迁移（TEM）过程中的作用尚不清楚。我们通过人肺微血管内皮细胞（HLMVECs）单层研究了β3整合素在PC3人前列腺癌细胞TEM中的作用。
用β3整合素抗体或反义核苷酸处理PC3细胞，并使用共聚焦显微镜评估其穿过内皮细胞（ECs）单层的迁移效率。
PC3细胞中的β3整合素不在粘着斑中定位，其阻断在迁移后期优先显著抑制TEM超过50%。β3整合素反义寡核苷酸显著减少了PC3细胞在基质胶上伪足的形成。
β3整合素在PC3细胞TEM过程中与内皮细胞下方的基质相互作用时发挥重要作用。这些相互作用与将β3整合素聚集到粘着斑的能力无关。
