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ADAM-17 是肝门部胆管癌患者的预后不良指标，受 FoxM1 调控。

ADAM-17 is a poor prognostic indicator for patients with hilar cholangiocarcinoma and is regulated by FoxM1.

机构信息

Department of Medical Oncology, Changzheng Hospital, Shanghai, China.

Department of Surgery, Eastern Hepatobiliary Surgery Hospital, Shanghai, China.

出版信息

BMC Cancer. 2018 May 18;18(1):570. doi: 10.1186/s12885-018-4294-9.

DOI:10.1186/s12885-018-4294-9
PMID:29776401
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC5960197/
Abstract

BACKGROUND

A-disintegrin and metalloproteinases (ADAMs) are members of a family of multidomain transmembrane and secreted proteins. Specific ADAMs are upregulated in human cancers and correlated with tumor progression and poor outcome, but rarely studied in human hilar cholangiocarcinoma (HC). This study aimed to explore the expression profiles of ADAMs and their potential underlying mechanisms promoting cancer progression.

METHODS

mRNA expression of ADAM-9, - 10, - 11, - 12, - 15, - 17, - 28, and - 33 was analyzed in human hilar cholangiocarcinoma (HC) samples. Immunohistochemical (IHC) analysis was used to detect the expression of ADAM-10, - 17, - 28, and FoxM1 in HC. The regulation of ADAM-17 by FoxM1 and their functional study was investigated in vivo and in vitro.

RESULTS

ADAM-10, - 17, and - 28 were upregulated in tumors compared with matched non-cancerous tissues. IHC analysis revealed increased expression of ADAM-10, - 17, and - 28 in HC cells, and ADAM17 seems to be an independent prognostic factor. ADAM-17 is regulated by FoxM1. A decrease in the expression of ADAM-17 by silencing FoxM1 led to an inhibition of cell proliferation, tumor growth, and the production of tumor necrosis factor α. IHC analysis showed co-expression of FoxM1 and ADAM-17 in HC specimens.

CONCLUSIONS

The findings of the present study show an important role of the cross-talk among FoxM1, ADAM-17, and TNFa in HC development and progression.

摘要

背景

解整合素金属蛋白酶（ADAMs）是一类具有多种结构域的跨膜和分泌蛋白家族的成员。特定的 ADAMs 在人类癌症中上调，并与肿瘤进展和不良预后相关，但在人类肝门部胆管癌（HC）中很少研究。本研究旨在探讨 ADAMs 的表达谱及其潜在的促进癌症进展的机制。

方法

分析了人肝门部胆管癌（HC）样本中 ADAM-9、-10、-11、-12、-15、-17、-28 和 -33 的 mRNA 表达。免疫组织化学（IHC）分析用于检测 ADAM-10、-17、-28 和 FoxM1 在 HC 中的表达。在体内和体外研究了 FoxM1 对 ADAM-17 的调节及其功能。

结果

与匹配的非癌组织相比，ADAM-10、-17 和 -28 在肿瘤中上调。IHC 分析显示 ADAM-10、-17 和 -28 在 HC 细胞中的表达增加，ADAM17 似乎是一个独立的预后因素。ADAM-17 受 FoxM1 调节。沉默 FoxM1 导致 ADAM-17 表达减少，从而抑制细胞增殖、肿瘤生长和肿瘤坏死因子 α 的产生。IHC 分析显示 FoxM1 和 ADAM-17 在 HC 标本中存在共表达。

结论

本研究的结果表明，FoxM1、ADAM-17 和 TNFa 之间的相互作用在 HC 的发生和发展中起着重要作用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6b67/5960197/bd8f596d76ce/12885_2018_4294_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6b67/5960197/a9f1b8451e2b/12885_2018_4294_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6b67/5960197/aeb63664f66c/12885_2018_4294_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6b67/5960197/4edb35160adb/12885_2018_4294_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6b67/5960197/b6ed97ddfcbb/12885_2018_4294_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6b67/5960197/bd8f596d76ce/12885_2018_4294_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6b67/5960197/a9f1b8451e2b/12885_2018_4294_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6b67/5960197/aeb63664f66c/12885_2018_4294_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6b67/5960197/4edb35160adb/12885_2018_4294_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6b67/5960197/b6ed97ddfcbb/12885_2018_4294_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6b67/5960197/bd8f596d76ce/12885_2018_4294_Fig5_HTML.jpg

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