Abstract
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.
Highlights
Pancreatic cancer is one of the most malignant neoplasms among all gastrointestinal cancers, with a 5-year survival rate below 6% and a median survival period of less than 6 months [1, 2]
Because leptin exerts its biological effects via binding to specific receptors [21], we first determined whether leptin receptors (Ob-Rs) existed in the human pancreatic cancer cells PANC-1 and AsPC-1
We investigated the influence of leptin on the proliferation of human pancreatic cancer cells
Summary
Pancreatic cancer is one of the most malignant neoplasms among all gastrointestinal cancers, with a 5-year survival rate below 6% and a median survival period of less than 6 months [1, 2]. Obesity has been associated with increased lymph node (LN) metastasis in patients with resected pancreatic cancer [7]. Both obesity and diabetes have been associated with decreased survival among pancreatic cancer patients [7, 8]. As an important adipocyte-derived peptide hormone, leptin functions in regulating food intake and energy metabolism [13]. Given that obesity and diabetes have been associated with the development of numerous cancers [19, 20], leptin may act as a link between metabolic disorders and cancer
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