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

Lumican对生长因子介导的胰腺癌细胞生长的抑制作用

基本信息

批准号：
18591526
负责人：
ISHIWATA Toshiyuki
金额：
$ 2.11万
依托单位：
Nippon Medical School
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
2006
资助国家：
日本
起止时间：
2006 至 2007
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-18591526/
关键词：
Lumican pancreatic cancer Growth factor glycosylation

项目摘要

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.

Lumican是一个富含亮氨酸的小蛋白聚糖家族的成员，并且在类癌肿瘤和乳腺，结直肠癌，神经内分泌细胞，子宫宫颈和胰腺癌中据报道其过表达。乳腺癌中基质组织中发光症的表达与高肿瘤级，低雌激素受体表达水平和年轻年龄有关。此外，晚期结直肠癌细胞质中的Lumican表达与淋巴结转移和肿瘤浸润深度的扩散弱相关，并且与预后不良密切相关。反转录聚合酶链反应（RT-PCR）和Western印迹分析表明，在六个胰腺导管腺癌（PDAC）细胞系（即Panc-1，MiaPACA-2，KLM-1，KLM-1，CAPAN-1，PKAN-1，PKAN-1，PK-1和PK-1和PK-8）中表现出Lumican mRNA和蛋白表达。 Lumican在胰腺癌细胞细胞质中的分子量为37至100KD，但细胞培养上清液中的Lumican为60-70KD。在胰腺癌组织中，在53例（56.6％）癌症患者中，有30名卢米卡（Lumican）位于癌细胞的细胞质中，而53例（67.9％）癌症患者中有36例在基质组织中检测到卢米卡。胰腺癌细胞细胞质中的Lumican表达与临床病理学因素无关，而基质组织中的Lumican表达与雌性性别，晚期，后阶段，腹膜后和十二指肠侵袭和残留肿瘤相关。 Lumican阳性癌细胞的患者的生存时间比患有Lumican阴性癌细胞的患者（P = 0.286），但具有Lumican阳性基质组织的患者比具有Lumican阴性基质组织的患者的存活率较短。这些发现表明，癌细胞和基质组织中的Lumican在基质组织中具有不同的糖基化模式，而Lumican在胰腺癌的生长和侵袭中起着重要作用。