Inhibitory effect of lumican on the growth factor-mediated pancreatic cancer cell growth

Lumican是一个小的富含亮氨酸的蛋白多糖家族的成员，其过表达已被报道在类癌、乳腺癌、结直肠癌、神经内分泌细胞、子宫癌和胰腺癌中。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、发病年龄小有关。此外，晚期结直肠癌细胞质中lumican的表达与淋巴结转移的扩散和肿瘤侵袭的深度呈弱相关，而与预后不良密切相关。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（即PDAC）中有lumican mRNA和蛋白的表达。PANC-1, MIA PaCa-2, KLM-1, Capan-1， PK-1和PK-8)。胰腺癌细胞细胞质中lumican分子量为37 ~ 100kD，细胞培养上清中lumican分子量为60 ~ 70kd。在胰腺癌组织中，53例患者中有30例（56.6%）存在于癌细胞的细胞质中，而53例患者中有36例（67.9%）存在于间质组织中。胰腺癌细胞质中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以及肿瘤残留有关。lumican阳性肿瘤细胞比lumican阴性肿瘤细胞存活时间更长（p=0.286），而lumican阳性间质组织比lumican阴性间质组织存活时间短。这些发现提示癌细胞和间质组织中的lumican具有不同的糖基化模式，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 and in 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 at on set. Furthermore, lumican expression in the cytoplasm in advanced colorectal cancer is weakly correlated with the spread of lymph node metastasis and depth of tumor invasion, and strongly correlated with a poor prognosis. Reverse-transcription polymerase chain reaction (RT-PCR) and Western blot analyses demonstrated lumican mRNA and protein expression in six pancreatic ductal adenocarcinoma (PDAC) cell lines (ie. PANC-1, MIA PaCa-2, KLM-1, Capan-1, PK-1 and PK-8). Molecular weights of lumican in the cytoplasm of pancreatic cancer cells were 37 to 100kD, but lumican in the culture supernatant of the cells was 60-70kD. In pancreatic cancer tissues, lumican was localized in the cytoplasm of cancer cells in 30 of 53 (56.6%) cancer patients, whereas lumican was detected in stromal tissues in 36 of 53 (67.9%) cancer patients. Lumican expression in the cytoplasm of pancreatic cancer cells did not correlate with clinicopathological factors, whereas lumican expression in stromal tissues correlated with female gender, advanced stage, retroperitoneal and duodenal invasion, and residual tumor. 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 showed a shorter survival than those with lumican-negative stromal tissues. These findings suggest that lumican in cancer cells and stromal tissues have different glycosylated patterns and lumican in stromal tissues play important roles in the growth and invasion of pancreatic cancer.