Expression of core 2 β1,6-N-acetylglucosaminyltransferase facilitates prostate cancer progression
Expression of core 2 β1,6-N-acetylglucosaminyltransferase facilitates prostate cancer progression
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DOI：
10.1093/glycob/cwi086
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发表时间：
2005-10-01
期刊：
影响因子：
4.3
通讯作者：
Fukuda, M
中科院分区：
文献类型：
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作者：
Hagisawa, S;Ohyama, C;Fukuda, M
上皮细胞上表达的细胞表面碳水化合物被认为在肿瘤进展中起重要作用。以前，我们已经表明，核心2-分支O-聚糖的表达与结肠癌和肺癌的血管浸润和浸润深度密切相关。在这项研究中，我们发现核心2 β 1，6-N-乙酰葡糖胺转移酶-1（Core 2GnT）的表达与人类患者前列腺癌的进展呈正相关。统计学分析表明，Core 2GnT是进展性病理分期（pT 3）和前列腺特异性抗原（PSA）复发的独立预测因子。为了直接确定Core 2GnT在前列腺癌进展中的作用，我们使用LNCaP前列腺癌细胞系建立了实验肿瘤模型。由于该株系不表达Core 2GnT，我们通过克隆编码Core 2GnT的cDNA，建立了稳定表达Core 2GnT的LNCaP株系，LNCap-Core 2GnT。当模拟转染的LNCaP细胞和LNCaP-Core 2GnT接种在裸鼠前列腺中时，LNCaP-Core 2GnT细胞产生的前列腺肿瘤比模拟转染的LNCaP细胞重三倍。此外，我们发现LNCaP-Core 2GnT细胞比LNCaP-mock细胞更强烈地粘附于前列腺基质细胞、IV型胶原和层粘连蛋白，但是LNCaP和LNCaP-Core 2GnT细胞在用IV型胶原或层粘连蛋白包被的板上几乎以相同的速率生长。这些结果表明，Core 2GnT是前列腺癌进展的一个非常有用的预后标志物。结果还表明，在前列腺癌细胞中获得Core 2GnT有助于粘附到IV型胶原和层粘连蛋白，这种粘附增加可能是表达Core 2GnT的前列腺癌细胞形成侵袭性肿瘤的原因。
Cell surface carbohydrates expressed on epithelial cells are thought to play an important role in tumor progression. Previously, we have shown that expression of core 2-branched O-glycans is closely correlated with vessel invasion and depth of invasion in colon and lung carcinomas. In this study, we found that expression of core 2 beta 1,6-N-acetylglucosaminyltransferase-1, Core2GnT, is positively correlated with the progression of prostate cancer in human patients. Statistical analysis demonstrated that Core2GnT is an independent predictor for progressed pathological stage (pT3) and for prostate-specific antigen (PSA) relapse. To determine directly the roles of Core2GnT in prostate cancer progression, we set up an experimental tumor model using the LNCaP prostate cancer cell line. Because this line does not express Core2GnT, we established an LNCaP line stably expressing Core2GnT, LNCap-Core2GnT, by transfecting cDNA encoding Core2GnT. When mock-transfected LNCaP cells and LNCaP-Core2GnT were inoculated in the prostate of nude mice, LNCaP-Core2GnT cells produced three times heavier prostate tumors than mock-transfected LNCaP cells. Furthermore, we found that LNCaP-Core2GnT cells adhered more strongly to prostate stromal cells, type IV collagen and laminin than did LNCaP-mock cells, but LNCaP and LNCaP-Core2GnT cells grew almost at the same rate on plates coated with type IV collagen or laminin. These results indicate that Core2GnT is an extremely useful prognostic marker for prostate cancer progression. The results also suggest that acquiring Core2GnT in prostate carcinoma cells facilitates adhesion to type IV collagen and laminin, and this increased adhesion may be a cause for aggressive tumor formation by prostate cancer cells expressing Core2GnT.