Expression of a human cell adhesion molecule, MUC18, in prostate cancer cell lines and tissues.

Abstract

Over expression of huMUC18, a cell adhesion molecule in the immunoglobulin gene superfamily, causes a non-metastatic human melanoma cell line to become metastatic in a nude mouse system. To determine if MUC18 expression correlates with the malignant progression of prostate cancer, we investigated differential expression of human MUC18 (huMUC18) in normal prostate epithelial cells, prostate cancer cell lines, and prostatic normal and cancer tissues. RT-PCR and Western blot analyses were used to analyze the expression of MUC18 mRNA and protein in four human prostate cancer cell lines, cultured primary normal prostate epithelial cells, normal prostate and malignant prostate tissues. Immunohistochemistry was used to determine the expression of MUC18 antigen in prostatic tissues at different stages of malignancy. Human MUC18 mRNA and protein was expressed in three different prostate cancer cell lines (TSU-PR1, DU145, and PC-3), but not in one prostate cancer cell line (LNCaP.FGC). HuMUC18 protein was also expressed at high levels in extracts prepared from tissue sample sections containing high grade prostatic intraepithelial neoplasia (PIN), but weakly expressed in extracts prepared from either cultured primary normal prostatic epithelial cells or the normal prostate gland. Immunohistochemical analysis showed that huMUC18 was expressed at higher levels in the epithelial cells of high-grade PIN and prostatic carcinomas and in cells of a lymph node metastasis compared to that in normal or benign hyperplastic epithelium (BPH). We therefore conclude that MUC18 is expressed at higher levels in pre-malignant and malignant prostatic epithelium, including metastasis. We suggest that over-expression of MUC18 may be a new marker of human prostate cancer and also implicates its possible role in development and progression of prostate cancer.