Role of lumican for cell growth and differentiation in pancreatic cancer

Lumican是一个小的富含亮氨酸的蛋白多糖家族的成员，它的过表达在乳腺癌、结直肠癌、子宫癌和胰腺癌中都有报道。乳腺癌间质组织中lumican的表达与肿瘤分级高、雌激素受体表达水平低、年龄小有关。晚期结直肠癌细胞质中Lumican的表达与预后不良相关。Lumican的表达先前在胰腺癌和邻近间质组织中有报道。逆转录聚合酶链反应（RT-PCR）和Western blot分析显示，6种胰腺导管腺癌（PDAC）细胞系（PANC-1、MIA PaCa-2、KLM-1、Capan-1、PK-1和PK-8）中有lumican mRNA和蛋白的表达。根据其免疫反应性，发现lumican定位于正常胰腺组织的胰岛细胞。在胰腺癌组织中，53例癌症患者中有30例（57%）存在于癌细胞的细胞质中，而53例癌症患者中有36例（68%）存在于间质组织中。胰腺癌细胞中Lumican的表达与临床病理因素无关，而间质组织中Lumican的表达与女性、晚期、腹膜后和十二指肠浸润相关。lumican阳性基质组织患者存活时间短于lumican阴性基质组织患者。这些结果提示间质组织中肿瘤细胞在胰腺癌的生长和侵袭中起重要作用。不同的糖基化侧链可能存在于癌细胞和邻近间质组织的细胞质中。

Lumican is a member of a small leucine-rich proteoglycan family and its overexpression has been reported in breast, colorectal, 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 correlated with poor prognosis. Lumican expression was previously reported in pancreatic cancer and adjacent stromal tissues. Reverse-transcription polymerase chain reaction (RT-PCR) and Western blot analyses revealed lumican mRNA and protein expression in six pancreatic ductal adenocarcinoma (PDAC) cell lines (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. In pancreatic cancer tissues, lumican was localized in the cytoplasm of cancer cells in 30 of 53 (57%) cancer patients, whereas lumican was detected in stromal tissues in 36 of 53 (68%) 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. Patients with lumican-positive stromal tissues survived shorter than those with lumican-negative stromal tissues. These results suggest that lumican in stromal tissues play important roles in the growth and invasion of pancreatic cancer. Different glycosylated side chains of lumican may present in cytoplasm of cancer cells and adjacent stromal tissues.