CD10+ Pancreatic Stellate Cells Enhance the Progression of Pancreatic Cancer
CD10+ Pancreatic Stellate Cells Enhance the Progression of Pancreatic Cancer
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DOI：
10.1053/j.gastro.2010.05.084
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发表时间：
2010-09-01
期刊：
影响因子：
29.4
通讯作者：
Tanaka, Masao
中科院分区：
文献类型：
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作者：
Ikenaga, Naoki;Ohuchida, Kenoki;Tanaka, Masao
背景与目的：胰腺星状细胞（Pancreatic stellate cells, PSCs）通过产生细胞外基质和可溶性因子促进胰腺癌的进展。然而，到目前为止，PSCs的功能异质性尚未被确定。人类胰腺癌中PSCs的详细表征将为基质定向治疗提供一组潜在靶点。方法：从新鲜胰腺导管腺癌组织中分离PSCs，根据细胞表面CD10的表达进行流式细胞术分选，CD10是各种肿瘤的间质预后标志物。我们分析了CD10(+) PSCs和CD10(-) PSCs之间的功能差异。结果：免疫组化分析显示，肿瘤组织中PSCs表达CD10的频率明显高于正常组织（33.7% vs 0%, P = 0.028）。在胰腺导管腺癌中，PSCs表达CD10与淋巴结转移阳性（P = 0.011）和较短的生存时间相关（P < 0.001）。体外共培养实验表明，CD10(+) PSCs比CD10(-) PSCs更强烈地促进胰腺癌细胞系、SUIT-2和Panc-1细胞的侵袭性。在小鼠共移植模型中，CD10(+) PSCs显著增加了SUIT-2细胞的肿瘤生长和侵袭性。CD10(+) PSCs分泌的基质金属蛋白酶3水平高于CD10(-) PSCs，共培养的PSCs中基质金属蛋白酶3的敲低可减少SUIT-2和Panc-1细胞的侵袭。结论：CD10(+) PSCs促进胰腺癌细胞的进展。CD10(+) PSCs可能是胰腺癌治疗中选择性靶向治疗的候选药物。
BACKGROUND & AIMS: Pancreatic stellate cells (PSCs) promote the progression of pancreatic cancer by producing extracellular matrix and soluble factors. However, the functional heterogeneity of PSCs has not been identified until now. Detailed characterization of the PSCs in human pancreatic cancer would provide a set of potential targets for stroma-directed therapy. METHODS: We isolated PSCs from fresh pancreatic ductal adenocarcinoma tissue and sorted them by flow cytometry according to cell surface expression of CD10, which is a stromal prognostic marker for various tumors. We analyzed the functional differences between CD10(+) PSCs and CD10(-) PSCs. RESULTS: Immunohistochemical analysis showed that the frequency of CD10 expression by PSCs was markedly higher in tumor tissue than in normal tissue (33.7% vs 0%, respectively, P = .028). In pancreatic ductal adenocarcinoma, CD10 expression by PSCs was associated with positive nodal metastases (P = .011) and a shorter survival time (P < .001). In vitro coculture experiments showed that CD10(+) PSCs promoted the invasiveness of pancreatic cancer cell lines, SUIT-2 and Panc-1 cells more intensively than CD10(-) PSCs. CD10(+) PSCs significantly increased the tumor growth and invasiveness of SUIT-2 cells in a murine co-transplantation model. CD10(+) PSCs secreted higher levels of matrix metalloproteinase 3 than CD10(-) PSCs, and knockdown of matrix metalloproteinase 3 in cocultured PSCs reduced the invasion of SUIT-2 and Panc-1 cells. CONCLUSIONS: CD10(+) PSCs enhance the progression of pancreatic cancer cells. CD10(+) PSCs may be a candidate for selective therapeutic targeting in the treatment of pancreatic cancer.