Pacis R, Pilat M, Yamazaki K, Pienta K
DEPT INTERNAL MED,DIV HEMATOL & ONCOL,ANN ARBOR,MI 48109. UNIV MICHIGAN,CTR COMPREHENS CANC,MICHIGAN PROSTATE INST,ANN ARBOR,MI.
Int J Oncol. 1995 Dec;7(6):1349-54. doi: 10.3892/ijo.7.6.1349.
Death from prostate cancer is most frequently a result of metastatic disease. A key step in the process of metastasis is the attachment of circulatory tumor cells to target organ endothelium. This process is thought to be mediated by lectins, a class of cell surface proteins that bind two or more carbohydrate groups. Using fluorescent microscopy and fluorescein isothiocyanate (FITC) conjugated lectins, the presence of various carbohydrates was examined in the following tumorigenic and non-tumorigenic cell lines: rat prostate epithelial (EPYP-2, EPYP-1), rat prostate endothelial (YPEN-2, YPEN-1, YPEN-2PV), Dunning rat prostate cancer cell lines (MLL, ML, AT6.3, AT.1, AT2.1, GP9F3), and three tumorigenic human prostate cell lines (LNCaP, PC3, PC3 bone). The lectin Triticum vulgaris (WGA) was found to readily bind the carbohydrates N-acetylglucosamine and sialic acid on the plasma membrane of tumorigenic cell lines. Interestingly, WGA bound carbohydrates located to the nucleus and cytoplasm in non-tumorigenic cell lines, indicating that N-acetylglucosamine and sialic acid residues are preferentially expressed on the cell membrane of prostate cancer cells. Lectin staining patterns in cell lines of varying metastatic potential revealed no significant difference between highly metastatic vs. low metastatic cell lines. Observations revealed an absence of N-acetylgalactosamine and L-fucose in all rat Dunning, epithelial and endothelial cell lines as well as all human prostate cancer cell lines except for the androgen insensitive human prostate cancer cell line PC3, in which L-fucose residues were detected in the nucleus and on the plasma membrane. PC3 bone cells, which metastasized selectively to bone, demonstrated the presence of galactose residues whereas PC3 cells did not, suggesting that preference for target organ endothelium may be influenced by the expression of carbohydrate residues. These data indicate that differential carbohydrate expression may play an important role in prostate cancer biology.
前列腺癌导致的死亡大多是转移性疾病所致。转移过程中的一个关键步骤是循环肿瘤细胞附着于靶器官内皮。这一过程被认为是由凝集素介导的,凝集素是一类能结合两个或更多碳水化合物基团的细胞表面蛋白。利用荧光显微镜和异硫氰酸荧光素(FITC)偶联凝集素,检测了以下致瘤和非致瘤细胞系中各种碳水化合物的存在情况:大鼠前列腺上皮细胞系(EPYP - 2、EPYP - 1)、大鼠前列腺内皮细胞系(YPEN - 2、YPEN - 1、YPEN - 2PV)、邓宁大鼠前列腺癌细胞系(MLL、ML、AT6.3、AT.1、AT2.1、GP9F3)以及三种致瘤性人前列腺细胞系(LNCaP、PC3、PC3 bone)。发现凝集素小麦胚芽凝集素(WGA)能轻易结合致瘤细胞系质膜上的碳水化合物N - 乙酰葡糖胺和唾液酸。有趣的是,WGA在非致瘤细胞系中结合位于细胞核和细胞质中的碳水化合物,这表明N - 乙酰葡糖胺和唾液酸残基在前列腺癌细胞的细胞膜上优先表达。不同转移潜能细胞系中的凝集素染色模式显示,高转移性细胞系和低转移性细胞系之间无显著差异。观察发现,除了雄激素不敏感的人前列腺癌细胞系PC3(在其细胞核和质膜中检测到L - 岩藻糖残基)外,所有大鼠邓宁、上皮和内皮细胞系以及所有人前列腺癌细胞系中均不存在N - 乙酰半乳糖胺和L - 岩藻糖。选择性转移至骨的PC3 bone细胞显示存在半乳糖残基,而PC3细胞则没有,这表明对靶器官内皮的偏好可能受碳水化合物残基表达的影响。这些数据表明,碳水化合物表达差异可能在前列腺癌生物学中起重要作用。