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

Lumcan是富含亮氨酸的蛋白多糖家族的一员。我们以前报道过LUMICA主要定位于病理性纤维化区域，包括人类冠状动脉内膜增厚、缺血和再灌流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，LUMICA的低表达水平与肿瘤进展快、生存率低有关。在实验上，鲁米能显著抑制同基因小鼠皮下肿瘤的形成，并伴随着细胞周期蛋白D1表达水平的降低，并诱导和/或促进这些细胞的凋亡。吗啉反义寡核苷酸对人胚胎肾(HEK)293细胞LUMICAN蛋白的合成有明显的抑制作用，且细胞生长速度明显高于对照组。这些结果可能表明鲁米肯蛋白在体外对HEK 293细胞的生长有抑制作用。本研究检测了LUMICA在神经内分泌(NE)细胞肿瘤(包括类癌和NE癌)中的表达，并探讨了LUMICA的存在是否与NE肿瘤的生长有关。免疫组织化学染色显示，瘤细胞胞浆中LUMANIC表达阳性率在类癌中为87.5%，在NE癌中为37.5%。癌旁间质的阳性表达在类癌中为90.1%，在NE癌中为79.2%。类癌中胞浆Lumcan的表达水平高于NE癌，可能是这些肿瘤生长缓慢的原因之一。进一步的研究，包括给胰腺癌细胞或实验癌症动物注射重组鲁米肯蛋白，可能会有效地检查鲁米肯在癌症治疗中的临床应用。

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.