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 nasopharyngealcarcinoma (NPC) remains unclear. To initiate the study we determined human METCAM/MUC18 expression intissue 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, 94NPC tissue specimens, and 3 metastatic lesions. Human METCAM/MUC18 was expressed in 100% of the normalNP, 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 NPCtissues 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 establishedNPC cell lines. These findings provided the first evidence that diminished expression of human METCAM/MUC18is 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 metastasispromoter for NPC.