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学科主题临床医学
Anti-inflammatory macrophages activate invasion in pancreatic adenocarcinoma by increasing the MMP9 and ADAM8 expression
Puolakkainen, Pauli1; Koski, Aino1; Vainionpaa, Sanna1; Shen, Zhanlong2,3; Repo, Heikki4; Kemppainen, Esko1; Mustonen, Harri1; Seppanen, Hanna1
关键词Pancreatic cancer Tumor-associated macrophages Hypoxia ADAM8 expression
刊名MEDICAL ONCOLOGY
2014-03-01
DOI10.1007/s12032-014-0884-9
31期:3
收录类别SCI
文章类型Article
WOS标题词Science & Technology
类目[WOS]Oncology
研究领域[WOS]Oncology
关键词[WOS]TUMOR-ASSOCIATED MACROPHAGES ; NF-KAPPA-B ; GASTRIC-CANCER ; DUCTAL ADENOCARCINOMA ; CELLS ; GROWTH ; MATRIX ; CARCINOMA ; PATHWAYS ; MATRIX-METALLOPROTEINASE-9
英文摘要

Patients with chronic pancreatitis with local inflammation have high risk for pancreatic cancer. The aim of this study was to examine the role of the inflammatory cells in the invasion of pancreatic cancer cells, focusing on the involvement of a disintegrin and metalloproteinase 8 (ADAM8) and matrix metalloproteinase 9 (MMP9) proteins. ADAM8 expression is associated with worse survival of pancreatic cancer patients. Monocytes from healthy donors were differentiated into macrophages. Pancreatic adenocarcinoma cells were cultured either alone or with differentiated macrophages. The cancer cell migration rate in Matrigel was measured by imaging fluorescently stained cells for 24 h. After invasion, cells were sorted into CD14 positive/negative macrophages and cancer cells with magnetic separation. The expression of ADAM8 and MMP9 was measured by the real-time PCR. Protein-level expression of ADAM8 and MMP9 was analyzed by Western blotting. In two series, siRNA technique was used to reduce either ADAM8 or MMP9 expression in the cancer cells. The coculture with macrophages increased cancer cell migration rate in Matrigel, and increased ADAM8 and MMP9 mRNA expression and protein level in the cancer cells. Reduction of ADAM8 expression with siRNA in the cancer cells decreased macrophage-induced migration rate of the cancer cells from 11.7 +/- 0.3 mu m/h to 9.0 +/- 0.2 mu m/h (p < 0.01), and reduction of MMP9 expression decreased the migration rate to 10.1 +/- 0.2 mu m/h (p < 0.01). Antiinflammatory macrophages increase pancreatic cancer cell migration rate in basement membrane matrix by inducing ADAM8 and MMP9 expression in cancer cells, thereby possibly enhancing the invasiveness of cancer.

语种英语
WOS记录号WOS:000337728700042
资助机构Georg C Ehrnrooth foundation ; Sigrid Juselius Foundation ; Helsinki University Central Hospital Research Funds
引用统计
被引频次:12[WOS]   [WOS记录]     [WOS相关记录]
文献类型期刊论文
条目标识符http://ir.bjmu.edu.cn/handle/400002259/58210
专题北京大学第二临床医学院_胃肠外科
作者单位1.Univ Helsinki, Dept Surg, Helsinki Univ Cent Hosp, Helsinki 00029, Finland
2.Peking Univ Peoples Hosp, Dept Surg Gastroenterol, Beijing, Peoples R China
3.Peking Univ Peoples Hosp, Dept Surg Oncol, Beijing, Peoples R China
4.Univ Helsinki, Dept Bacteriol & Immunol, Hartmann Inst, Helsinki 00029, Finland
推荐引用方式
GB/T 7714
Puolakkainen, Pauli,Koski, Aino,Vainionpaa, Sanna,et al. Anti-inflammatory macrophages activate invasion in pancreatic adenocarcinoma by increasing the MMP9 and ADAM8 expression[J]. MEDICAL ONCOLOGY,2014,31(3).
APA Puolakkainen, Pauli.,Koski, Aino.,Vainionpaa, Sanna.,Shen, Zhanlong.,Repo, Heikki.,...&Seppanen, Hanna.(2014).Anti-inflammatory macrophages activate invasion in pancreatic adenocarcinoma by increasing the MMP9 and ADAM8 expression.MEDICAL ONCOLOGY,31(3).
MLA Puolakkainen, Pauli,et al."Anti-inflammatory macrophages activate invasion in pancreatic adenocarcinoma by increasing the MMP9 and ADAM8 expression".MEDICAL ONCOLOGY 31.3(2014).
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