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Role of lumican in pancreatic cancer and chronic pancreatits-like lesion in pancreatic cancer

Lumican 在胰腺癌和胰腺癌慢性胰腺样病变中的作用

基本信息

批准号：
15591449
负责人：
NAITO Zenya
金额：
$ 1.15万
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：
2003
资助国家：
日本
起止时间：
2003 至 2004
项目状态：
已结题

项目摘要

Lumican is a member of small leucine-rich proteoglycan family. We previously reported that lumican was predominantly localized in the area of pathological fibrosis including the thickened intima of human coronary arteries, ischemic and reperfused hearts, and acute pancreatitis and chronic pancreatitis(CP)-like lesions adjacent to pancreatic cancer. In the breast cancer tissues, low expression level of lumican is associated with a rapid cancer progression and poor survival. Experimentally, lumican significantly suppressed subcutanesous tumor formation in syngenic mice, with a concomitant decrease in cyclin D1 expression level, and induced and/or enhanced the apoptosis of these cells. Morpholino antisense oligonucleotide against lumican mRNA strongly inhibited the synthesis of lumican protein in the human embryonic kidney(HEK) 293 cells, and the HEK 293 cell growth rate was higher than those in the control groups. These findings may indicate that lumican protein has an inhibitory effect on HEK 293 cell growth in vitro. The expression of lumican in neuroendocrine(NE) cell tumors including carcinoid tumors and NE carcinoma were examined, and whether the presence of lumican may be associated with the growth of NE tumors were elucidated. Immunohistochemically, the positivity rates of lumican expression in the cytoplasm of the tumor cells were 87.5% in carcinoid tumors and 37.5% in NE carcinomas. Those of lumican expression in stromal adjacent to the tumors were 90.1% in carcinoid tumors and 79.2% in NE carcinomas. Higher expression level of cytoplasmic lumican in carcinoid tumors than in NE carcinomas may play a role in the slow growth of these tumors. Further studies, including administration of recombinant lumican protein to pancreatic cancer cells or experimental cancer animals may be effective to examine the clinical application of lumican to cancer therapy.

Lumican是富含亮氨酸的小分子蛋白聚糖家族的成员。我们先前报道，Lumican主要定位于病理性纤维化区域，包括人冠状动脉内膜增厚、缺血和再灌注心脏以及胰腺癌附近的急性胰腺炎和慢性胰腺炎（CP）样病变。在乳腺癌组织中，低表达水平的Lumican与快速的癌症进展和较差的存活率相关。实验上，Lumican显着抑制同系小鼠皮下肿瘤的形成，同时降低细胞周期蛋白D1的表达水平，并诱导和/或增强这些细胞的凋亡。Lumican mRNA的反义寡核苷酸能明显抑制人胚肾（HEK）293细胞中Lumican蛋白的合成，并使HEK 293细胞的生长速度高于对照组。这些发现可能表明Lumican蛋白在体外对HEK 293细胞生长具有抑制作用。检测了Lumican在神经内分泌（NE）细胞肿瘤（包括类癌肿瘤和NE癌）中的表达，并阐明了Lumican的存在是否与NE肿瘤的生长有关。免疫组化结果显示，类癌和NE癌细胞胞浆中Lumican阳性表达率分别为87.5%和37.5%。类癌癌旁间质Lumican阳性表达率为90.1%，NE癌为79.2%。类癌细胞胞浆光蛋白聚糖的表达水平高于NE癌细胞，这可能与类癌细胞生长缓慢有关。进一步的研究，包括给予胰腺癌细胞或实验性癌症动物重组lumican蛋白，可能有效地检查lumican在癌症治疗中的临床应用。