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肌球蛋白 1C 同工型 A 是前列腺癌的一种新型候选诊断标志物。

Myosin 1C isoform A is a novel candidate diagnostic marker for prostate cancer.

机构信息

School of Biology, Cell Biology and Histology Department, M.V. Lomonosov Moscow State University, Moscow, Russia.

A.N. Belozersky Institute of Physico-Chemical Biology, M.V. Lomonosov Moscow State University, Moscow, Russia.

出版信息

PLoS One. 2021 May 21;16(5):e0251961. doi: 10.1371/journal.pone.0251961. eCollection 2021.

Abstract

Early diagnosis of prostate cancer is a challenging issue due to the lack of specific markers. Therefore, a sensitive diagnostic marker that is expressed or upregulated exclusively in prostate cancer cells would facilitate diagnostic procedures and ensure a better outcome. We evaluated the expression of myosin 1C isoform A in 5 prostate cell lines, 41 prostate cancer cases, and 11 benign hyperplasias. We analyzed the expression of 12 surface molecules on prostate cancer cells by flow cytometry and analyzed whether high or low myosin 1C isoform A expression could be attributed to a distinct phenotype of prostate cancer cells. Median myosin 1C isoform A expression in prostate cancer samples and cancer cell lines was 2 orders of magnitude higher than in benign prostate hyperplasia. Based on isoform A expression, we could also distinguish clinical stage 2 from clinical stage 3. Among cell lines, PC-3 cells with the highest myosin 1C isoform A level had diminished numbers of CD10/CD13-positive cells and increased numbers of CD29 (integrin β1), CD38, CD54 (ICAM1) positive cells. The surface phenotype of clinical samples was similar to prostate cancer cell lines with high isoform A expression and could be described as CD10-/CD13- with heterogeneous expression of other markers. Both for cell lines and cancer specimens we observed the strong correlation of high myosin 1C isoform A mRNA expression and elevated levels of CD29 and CD54, suggesting a more adhesive phenotype for cells with high isoform A expression. Compared to normal tissue, prostate cancer samples had also reduced numbers of CD24- and CD38-positive cells. Our data suggest that a high level of myosin 1C isoform A is a specific marker both for prostate cancer cells and prostate cancer cell lines. High expression of isoform A is associated with less activated (CD24/CD38 low) and more adhesive (CD29/CD54 high) surface phenotype compared to benign prostate tissue.

摘要

前列腺癌的早期诊断是一个具有挑战性的问题,因为缺乏特异性标志物。因此,一种在前列腺癌细胞中特异性表达或上调的敏感诊断标志物将有助于诊断程序,并确保更好的结果。我们评估了肌球蛋白 1C 同工型 A 在 5 种前列腺细胞系、41 例前列腺癌病例和 11 例良性增生中的表达。我们通过流式细胞术分析了前列腺癌细胞 12 种表面分子的表达,并分析了高或低肌球蛋白 1C 同工型 A 的表达是否归因于前列腺癌细胞的独特表型。前列腺癌样本和癌细胞系中肌球蛋白 1C 同工型 A 的中位表达比良性前列腺增生高 2 个数量级。基于同工型 A 的表达,我们还可以区分临床分期 2 期和 3 期。在细胞系中,具有最高肌球蛋白 1C 同工型 A 水平的 PC-3 细胞中 CD10/CD13 阳性细胞数量减少,CD29(整合素β1)、CD38、CD54(ICAM1)阳性细胞数量增加。临床样本的表面表型与高同工型 A 表达的前列腺癌细胞系相似,可描述为 CD10-/CD13-,其他标志物呈异质性表达。对于细胞系和癌症标本,我们都观察到高肌球蛋白 1C 同工型 A mRNA 表达与 CD29 和 CD54 水平升高之间的强相关性,这表明高同工型 A 表达的细胞具有更黏附的表型。与正常组织相比,前列腺癌样本中 CD24-和 CD38-阳性细胞的数量也减少。我们的数据表明,高水平的肌球蛋白 1C 同工型 A 既是前列腺癌细胞又是前列腺癌细胞系的特异性标志物。与良性前列腺组织相比,同工型 A 的高表达与较少激活(CD24/CD38 低)和更黏附(CD29/CD54 高)的表面表型相关。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c785/8139512/85293e5c2ac0/pone.0251961.g001.jpg

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