Department of Medicine, Clinical Pharmacology and Therapeutics Unit, Austin Health, University of Melbourne, VIC, Australia.
Oncol Rep. 2010 Dec;24(6):1593-7. doi: 10.3892/or_00001022.
The molecular mechanisms underlying prostate cancer metastasis remain poorly understood. The tetraspanin family member CD151 has been reported as an 'adaptor' between integrins and signal pathways. The role of CD151 in prostate cancer metastasis in vitro was investigated in this study. LNCap cells were transfected with wild-type CD151 cDNA, mutated CD151 cDNA and vector cDNA. The mutant (QRD194-196 to INF) CD151 cDNA was created using QuickChange 2 site directed Mutagenesis kit (Stratagene). siRNAs were also used to knock down the CD151 expression in the prostate cancer cell line PC3. Proliferation, migration and invasion properties were measured after gene transfection and gene knock-down. There was no difference in proliferation of untransfected or control transfected LNCap cells vs. CD151 transfected LNCap cells (P>0.05). There was greater motility of CD151-transfected vs. control cells, when transferring through migration chambers with or without matrigel-coated membranes (P<0.01, P<0.01). Fewer numbers of mutant-transfected cells were found on the membranes for both migration and invasion studies (P<0.01, P<0.01). CD151 knock-down PC3 cells showed decreased motility (P<0.01), but no change in proliferation (P>0.05). Our data show that CD151 does not change the proliferative properties of prostate cancer cells, but does promote migration and invasion, and suggest that CD151 plays a specific role in promoting prostate cancer cell motility.
前列腺癌转移的分子机制仍知之甚少。四跨膜蛋白家族成员 CD151 已被报道为整合素和信号通路之间的“衔接子”。本研究旨在探讨 CD151 在前列腺癌细胞体外转移中的作用。用野生型 CD151 cDNA、突变型 CD151 cDNA 和载体 cDNA 转染 LNCap 细胞。使用 QuickChange 2 定点突变试剂盒(Stratagene)构建突变型(QRD194-196 至 INF)CD151 cDNA。还使用 siRNA 敲低前列腺癌细胞系 PC3 中的 CD151 表达。基因转染和基因敲低后测量增殖、迁移和侵袭特性。未转染或对照转染的 LNCap 细胞与转染 CD151 的 LNCap 细胞之间的增殖没有差异(P>0.05)。在有或没有基质胶包被膜的迁移室中转染 CD151 的细胞比对照细胞具有更强的迁移能力(P<0.01,P<0.01)。在迁移和侵袭研究中,转染突变体的细胞数量较少(P<0.01,P<0.01)。CD151 敲低的 PC3 细胞显示出迁移能力降低(P<0.01),但增殖没有变化(P>0.05)。我们的数据表明,CD151 不会改变前列腺癌细胞的增殖特性,但确实促进迁移和侵袭,表明 CD151 在促进前列腺癌细胞迁移中发挥特定作用。