期刊
ONCOTARGET
卷 6, 期 18, 页码 16120-16134出版社
IMPACT JOURNALS LLC
DOI: 10.18632/oncotarget.3878
关键词
leptin; metastasis; MMP-13; Ob-Rb; pancreatic cancer
资金
- State Key Laboratory of Oncogenes and Related Genes [91-10-03]
- Specialized Research Fund for the Doctoral Program of Higher Education of China [20120073120094]
- Innovation Program of Shanghai Municipal Education Commission [13YZ036]
Emerging evidence has suggested that leptin, an adipokine related to energy homeostasis, plays a role in cancer growth and metastasis. However, its impact on pancreatic cancer is rarely studied. In this study, we found that leptin's functional receptor Ob-Rb was expressed in pancreatic cancer cell lines. Treatment with leptin enhanced the migration and invasion of pancreatic cancer cells but did not affect the proliferation of human pancreatic cancer cells. Leptin up-regulated the expression of matrix metalloproteinase-13 (MMP-13) via the JAK2/STAT3 signaling pathway. The overexpression of leptin was shown to significantly promote tumor growth and lymph node metastasis in a subcutaneous model and an orthotopic model of human pancreatic cancer, respectively. Furthermore, in human pancreatic cancer tissues, the expression of Ob-Rb was positively correlated with the MMP-13 level. The increased expression of either Ob-Rb or MMP-13 was significantly associated with lymph node metastasis and tended to be associated with the TNM stage in patients with pancreatic cancer. Our findings suggest that leptin enhances the invasion of pancreatic cancer through the increase in MMP-13 production, and targeting the leptin/MMP-13 axis could be an attractive therapeutic strategy for pancreatic cancer.
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