Role of lumican in cancer cells and adjacent stromal tissues in human pancreatic cancer.
Role of lumican in cancer cells and adjacent stromal tissues in human pancreatic cancer.
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DOI：
10.3892/or.18.3.537
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发表时间：
2007-09
期刊：
影响因子：
4.2
通讯作者：
T. Ishiwata;Kazumitsu Cho;K. Kawahara;Tetsushi Yamamoto;Yuri Fujiwara;E. Uchida;T. Tajiri;Z. Naito
中科院分区：
文献类型：
--
作者：
T. Ishiwata;Kazumitsu Cho;K. Kawahara;Tetsushi Yamamoto;Yuri Fujiwara;E. Uchida;T. Tajiri;Z. Naito
Lumican是一个富含亮氨酸的蛋白聚糖小家族的成员，其过表达已在类癌、乳腺癌、结直肠癌、神经内分泌细胞癌、宫颈癌和胰腺癌中报道。Lumican在乳腺癌间质组织中的表达与高肿瘤分级、低雌激素受体表达水平和年轻相关。Lumican在进展期结直肠癌细胞质中的表达与预后不良相关。Lumican在胰腺癌中的表达以前曾有报道，但Lumican在胰腺癌中的作用仍不清楚。在这项研究中，我们的目的是阐明Lumican在胰腺癌中的作用。逆转录聚合酶链反应和蛋白质印迹分析揭示了六种胰腺导管腺癌细胞系（即PANC-1、MIA PaCa-2、KLM-1、Capan-1、PK-1和PK-8）中的lumican mRNA和蛋白质表达。基于其免疫反应性，发现Lumican定位于正常胰腺组织的胰岛细胞中，但不在外分泌细胞中。在胰腺癌组织中，在53名癌症患者中的30名（56.6%）中，Lumican主要定位于癌细胞的细胞质中，而在53名癌症患者中的36名（67.9%）中，在基质组织中检测到Lumican。Lumican在胰腺癌细胞中的表达与临床病理因素无关，而Lumican在间质组织中的表达与女性性别、晚期、腹膜后和十二指肠浸润以及残留肿瘤相关（p分别为0.030、0.038、0.049、0.049和0.048）。具有Lumican阳性癌细胞的患者倾向于比具有Lumican阴性癌细胞的患者存活更长（p=0.286），但是具有Lumican阳性基质组织的患者比具有Lumican阴性基质组织的患者存活更短（p=0.062）。这些结果表明，间质组织中的Lumican在胰腺癌的生长和侵袭中起重要作用。
Lumican is a member of a small leucine-rich proteoglycan family and its overexpression has been reported in carcinoid tumor, breast, colorectal, neuroendocrine cell, uterine cervical and pancreatic cancers. The expression of lumican in stromal tissues in breast cancer is associated with a high tumor grade, a low estrogen receptor expression level and young age. Lumican expression in the cytoplasm in advanced colorectal cancer is correlated with a poor prognosis. Lumican expression was previously reported in pancreatic cancer, but the role of lumican in pancreatic cancer is still not well understood. In this study, we aimed to clarify the role of lumican in pancreatic cancer. Reverse-transcription polymerase chain reaction and Western blot analyses revealed lumican mRNA and protein expression in six pancreatic ductal adenocarcinoma cell lines (i.e. PANC-1, MIA PaCa-2, KLM-1, Capan-1, PK-1 and PK-8). On the basis of its immunoreactivity, lumican was found to be localized in islet cells of normal pancreatic tissues, but not in exocrine cells. In pancreatic cancer tissues, lumican was predominantly localized in the cytoplasm of cancer cells in 30 out of 53 (56.6%) cancer patients, whereas lumican was detected in stromal tissues in 36 out of 53 (67.9%) cancer patients. Lumican expression in pancreatic cancer cells did not correlate with clinicopathological factors, whereas lumican expression in stromal tissues correlated with the female gender, advanced stage, retroperitoneal and duodenal invasion and residual tumor (p=0.030, 0.038, 0.049, 0.049 and 0.048, respectively). Patients with lumican-positive cancer cells tended to survive longer than those with lumican-negative cancer cells (p=0.286), but patients with lumican-positive stromal tissues had shorter survival than those with lumican-negative stromal tissues (p=0.062). These results suggest that lumican in stromal tissues plays an important role in the growth and invasion of pancreatic cancer.