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

Lumican是富含亮氨酸的小蛋白聚糖家族的一员。我们之前报道，lumican主要局限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，以及与胰腺癌相邻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与癌症的快速进展和较差的生存有关。实验表明，lumican显著抑制了同基因小鼠皮下肿瘤的形成，同时降低了cyclin D1的表达水平，并诱导和/或增强了这些细胞的凋亡。抗lumican mRNA的Morpholino反义寡核苷酸能强烈抑制人胚胎肾（HEK） 293细胞中lumican蛋白的合成，使HEK 293细胞的生长速率高于对照组。这些结果可能提示lumican蛋白在体外对HEK 293细胞生长具有抑制作用。我们检测了lumican在神经内分泌（NE）细胞肿瘤（包括类癌和NE癌）中的表达，并阐明lumican的存在是否与NE肿瘤的生长有关。免疫组化结果显示，肿瘤细胞胞质中lumican表达阳性率在类癌中为87.5%，在NE癌中为37.5%。类癌旁间质中lumican的表达率为90.1%，NE癌中为79.2%。类癌中细胞质腔细胞的表达水平高于NE癌，这可能是类癌生长缓慢的原因之一。进一步的研究，包括重组lumican蛋白给药于胰腺癌细胞或实验癌症动物，可能有效地检验lumican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.