Downregulation of osteopontin and bone sialoprotein II is related to reduced colony formation and metastasis formation of MDA-MB-231 human breast cancer cells
Downregulation of osteopontin and bone sialoprotein II is related to reduced colony formation and metastasis formation of MDA-MB-231 human breast cancer cells
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DOI：
10.1038/sj.cgt.7700659
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发表时间：
2004-02-01
影响因子：
6.4
通讯作者：
Berger, MR
中科院分区：
文献类型：
--
作者：
Adwan, H;Bäuerle, TJ;Berger, MR
骨桥蛋白（OPN）、骨唾液酸蛋白（BSPII）和骨粘连蛋白（ON）属于糖蛋白家族，它们与癌症的转移和进展有关。在这里，我们报告的选择反义寡核苷酸（ASO），这是有效地降低其蛋白质水平。在人MDA-MB-231乳腺癌细胞中，蛋白表达的最大抑制范围为84%（OPN）至75%（BSPII）和70%（ON）。使用芥酸磷酸-NNN-三甲基丙醇胺（ErPC 3）作为阳性对照和组合伴侣。暴露于ErPC 3抑制MDA-MB-231细胞的集落形成，抑制率分别为11%（10 μ M）、45%（14 μ M）和78%（20 μ M）。ASO-OPN-04、ASO-BSPII-06和ASO-ON-03分别使乳腺癌细胞的克隆形成能力降低15%、11%、8%（5 μ M）、39%、19%、14%（10 μ M）和46%、39%、21%（20 μ M）。ErPC 3与ASO的组合引起加性组合效应。ASO-OPN-04组中有3例溶骨性转移灶的形成受到ASO-OPN-04的抑制，而NSO组则无此作用（P
Osteopontin (OPN), bone sialoprotein (BSPII), and osteonectin (ON) belong to a family of glycoproteins, which have been linked to cancer metastasis and progression. Here, we report on the selection of antisense oligonucleotides (ASOs), which are effective in reducing their protein levels. In human MDA-MB-231 breast cancer cells, the maximum inhibition of protein expression ranged from 84% (OPN) to 75% (BSPII) and 70% (ON). Erucylphospho-NNN-trimethylpropanolamine (ErPC3) was used as positive control and combination partner. Exposure to ErPC3 inhibited colony formation of MDA-MB-231 cells by 11% (10 muM), 45% (14 muM) and 78% (20 muM). The clonogenicity of breast cancer cells was reduced by 15%, 11%, 8% (5 muM), 39%, 19%, 14% (10 muM) and 46%, 39%, 21% (20 muM) in response to ASO-OPN-04, ASO-BSPII-06 and ASO-ON-03, respectively. Combination of ErPC3 with the ASOs caused additive combination effects. Pre-exposure to the ASOs, but not to the NSO, inhibited formation of osteolytic metastasis in three of four (ASO-OPN-04, P