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肾上腺髓质素在卵巢上皮性癌中的表达及其促进 HO8910 细胞迁移的作用与上调整合素 α5β1 和磷酸化 FAK 和桩蛋白有关。

Adrenomedullin expression in epithelial ovarian cancers and promotes HO8910 cell migration associated with upregulating integrin α5β1 and phosphorylating FAK and paxillin.

机构信息

Department of Gynecology, The First Hospital of China Medical University, Shenyang, China.

出版信息

J Exp Clin Cancer Res. 2012 Mar 9;31(1):19. doi: 10.1186/1756-9966-31-19.

Abstract

BACKGROUND

Epithelial ovarian cancer (EOC) is one of the leading causes of cancer deaths in women worldwide. Adrenomedullin (AM) is a multifunctional peptide which presents in various kinds of tumors.

METHODS

In this study, we characterized the expression and function of AM in epithelial ovarian cancer using immunohistochemistry staining. Exogenous AM and small interfering RNA (siRNA) specific for AM receptor CRLR were treated to EOC cell line HO8910. Wound healing assay and flow cytometry were used to measure the migration ability and expression of integrin α5 of HO8910 cells after above treatments. Western blot was used to examine the phosphorylation of FAK and paxillin.

RESULTS

We found that patients with high AM expression showed a higher incidence of metastasis, larger residual size of tumors after cytoreduction and shorter disease-free and overall survival time. Exogenous AM induced ovarian cancer cell migration in time- and dose- dependent manners. AM upregulated the expression of integrin α5 and phosphorylation of FAK, paxillin as well.

CONCLUSIONS

Our results suggested that AM contributed to the progression of EOC and had additional roles in EOC cell migration by activating the integrin α5β1 signaling pathway. Therefore, we presumed that AM could be a potential molecular therapeutic target for ovarian carcinoma.

摘要

背景

上皮性卵巢癌(EOC)是全球女性癌症死亡的主要原因之一。肾上腺髓质素(AM)是一种多功能肽,存在于各种肿瘤中。

方法

本研究采用免疫组织化学染色法,研究 AM 在卵巢上皮性癌细胞中的表达和功能。用外源性 AM 和针对 AM 受体 CRLR 的小干扰 RNA(siRNA)处理卵巢癌细胞系 HO8910。用划痕愈合实验和流式细胞术检测上述处理后 HO8910 细胞的迁移能力和整合素 α5 的表达。用 Western blot 检测 FAK 和桩蛋白的磷酸化。

结果

我们发现 AM 高表达的患者转移发生率更高,细胞减灭术后肿瘤残余体积更大,无病生存期和总生存期更短。外源性 AM 以时间和剂量依赖的方式诱导卵巢癌细胞迁移。AM 还上调整合素 α5 的表达和 FAK、桩蛋白的磷酸化。

结论

我们的研究结果表明,AM 促进了 EOC 的进展,并通过激活整合素 α5β1 信号通路在上皮性卵巢癌细胞迁移中发挥了额外的作用。因此,我们推测 AM 可能成为卵巢癌的潜在分子治疗靶点。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f36c/3337271/acee9c7dd3fa/1756-9966-31-19-1.jpg

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