Lin Jin-Ching, Chiang Cheng-Feng, Wang Shur-Wern, Wang Wen-Yi, Kwan Po-Cheung, Wu Guang-Jer
Department of Radiation Oncology, Taichung Veterans General Hospital, Taichung, Taiwan E-mail :
Asian Pac J Cancer Prev. 2014;15(1):245-52. doi: 10.7314/apjcp.2014.15.1.245.
Human METCAM/MUC18, a cell adhesion molecule (CAM) in the immunoglobulin-like gene super family, plays a dual role in the progression of several epithelium cancers; however, its role in the nasopharyngeal carcinoma (NPC) remains unclear. To initiate the study we determined human METCAM/MUC18 expression in tissue samples of normal nasopharynx (NP), NPCs, and metastatic lesions, and in two established NPC cell lines. Immunoblotting analysis was used for the determination in lysates of frozen tissues, and immunohistochemistry (IHC) for expression in formalin-fixed, paraffin-embedded tissue sections of 7 normal nasopharynx specimens, 94 NPC tissue specimens, and 3 metastatic lesions. Human METCAM/MUC18 was expressed in 100% of the normal NP, not expressed in 73% of NPC specimens (or expressed at very low levels in only about 27% of NPC specimens), and expressed again in all of the metastatic lesions. The level of human METCAM/MUC18 expression in NPC tissues was about one fifth of that in the normal NP and metastatic lesions. The low level of human METCAM/ MUC18 expression in NPC specimens was confirmed by a weak signal of RT-PCR amplification of the mRNA. Low expression levels of human METCAM/MUC18 in NPC tissues were also reflected in the seven established NPC cell lines. These findings provided the first evidence that diminished expression of human METCAM/MUC18 is an indicator for the emergence of NPC, but increased expression then occurs with metastatic progression, suggesting that huMETCAM/MUC18, perhaps similar to TGF-β, may be a tumor suppressor, but a metastasis promoter for NPC.
人METCAM/MUC18是免疫球蛋白样基因超家族中的一种细胞粘附分子（CAM），在多种上皮癌的进展中发挥双重作用；然而，其在鼻咽癌（NPC）中的作用仍不清楚。为开展此项研究，我们测定了正常鼻咽（NP）、NPC及转移灶组织样本以及两种已建立的NPC细胞系中人METCAM/MUC18的表达。采用免疫印迹分析测定冷冻组织裂解物中的表达情况，采用免疫组织化学（IHC）检测7例正常鼻咽标本、94例NPC组织标本和3例转移灶的福尔马林固定石蜡包埋组织切片中的表达。人METCAM/MUC18在100%的正常NP中表达，在73%的NPC标本中不表达（或仅在约27%的NPC标本中以极低水平表达），而在所有转移灶中再次表达。NPC组织中人METCAM/MUC18的表达水平约为正常NP和转移灶中的五分之一。NPC标本中人METCAM/MUC18低表达通过mRNA的RT-PCR扩增弱信号得以证实。人METCAM/MUC18在NPC组织中的低表达水平在7种已建立的NPC细胞系中也有体现。这些发现首次证明人METCAM/MUC18表达降低是NPC出现的一个指标，但在转移进展时表达增加，这表明人METCAM/MUC18可能与转化生长因子-β类似，可能是一种肿瘤抑制因子，但却是NPC的转移促进因子。
