人 METCAM/MUC18 在癌组织和转移病灶中的频繁和增加的表达与人卵巢癌的临床进展有关。

Frequent and increased expression of human METCAM/MUC18 in cancer tissues and metastatic lesions is associated with the clinical progression of human ovarian carcinoma.

机构信息

Department of Microbiology & Immunology and The Winship Cancer Institute, Emory University School of Medicine, Rollins Research Center, Atlanta, GA 30322, USA; Department of Bioscience Technology, Chung Yuan Christian University, Chung Li 32023, Taiwan.

School of Biology and the Ovarian Cancer Institute, Georgia Institute of Technology, Atlanta, GA 30332, USA.

出版信息

Taiwan J Obstet Gynecol. 2014 Dec;53(4):509-17. doi: 10.1016/j.tjog.2014.03.003.

DOI:10.1016/j.tjog.2014.03.003

PMID:25510693

Abstract

OBJECTIVES

Human METCAM/MUC18 (huMETCAM/MUC18), a cell adhesion molecule, plays an important role in the progression of several epithelial cancers; however, its role in the progression of epithelial ovarian cancers is unknown. To initiate the study we determined expression of this protein in normal and cancerous ovarian tissues, cystadenomas, metastatic lesions, and ovarian cancer cell lines.

MATERIALS AND METHODS

Immunoblotting and immunohistochemical (IHC) methods were used to determine huMETCAM/MUC18 expression in lysates of frozen and formalin-fixed, paraffin-embedded tissue sections of normal human ovaries, and ovarian (benign) cystadenomas, carcinomas and metastatic lesions. We also determined expression levels of several downstream effectors of METCAM/MUC18 in these tissues.

RESULTS

HuMETCAM/MUC18 levels in ovarian carcinomas and metastatic lesions were significantly higher than in normal tissues and cystadenomas. IHC results showed that expression of huMETCAM/MUC18 in normal tissues and cystadenomas was mostly absent from epithelial cells, but in carcinomas and metastatic lesions it was localized to epithelial cells. In higher pathological grades of ovarian cancer and metastatic lesions, the percentage of cells stained in IHC was increased. Thirty percent of normal tissues weakly expressed the huMETCAM/MUC18 antigen, but 70% of cancer tissues and 100% of metastatic lesions expressed the antigen. Expression levels of several downstream effectors of huMETCAM/MUC18, Bcl2, PCNA and VEGF, were elevated in cancerous tissues, however, not that of Bax. The phospho-AKT/AKT ratio was elevated in metastatic lesions.

CONCLUSION

Upexpression of huMETCAM/MUC18 may be a marker for the malignant potential of ovarian carcinomas. Progression of ovarian cancer may involve increased signaling in anti-apoptosis, proliferation, survival/proliferation pathway, and angiogenesis.

摘要

目的

人 METCAM/MUC18（huMETCAM/MUC18）是一种细胞黏附分子，在几种上皮癌的进展中发挥着重要作用；然而，其在卵巢上皮癌进展中的作用尚不清楚。为了开展这项研究，我们检测了该蛋白在正常和癌变卵巢组织、囊腺瘤、转移灶以及卵巢癌细胞系中的表达情况。

材料与方法

我们采用免疫印迹和免疫组化（IHC）方法，检测了 huMETCAM/MUC18 在正常卵巢组织、卵巢（良性）囊腺瘤、癌组织及转移灶的冰冻和福尔马林固定石蜡包埋组织切片中的表达情况，还检测了这些组织中 huMETCAM/MUC18 的几种下游效应物的表达水平。

结果

卵巢癌和转移灶中的 huMETCAM/MUC18 水平明显高于正常组织和囊腺瘤。IHC 结果显示，huMETCAM/MUC18 在正常组织和囊腺瘤中的表达主要不存在于上皮细胞中，但在癌组织和转移灶中定位于上皮细胞。在卵巢癌和转移灶的较高病理分级中，IHC 染色的细胞百分比增加。30%的正常组织弱阳性表达 huMETCAM/MUC18 抗原，但 70%的癌组织和 100%的转移灶表达该抗原。huMETCAM/MUC18 的几种下游效应物，如 Bcl2、PCNA 和 VEGF 的表达水平在癌组织中升高，而 Bax 的表达水平则没有升高。磷酸化 AKT/AKT 比值在转移灶中升高。