Pancreatic Stellate Cells Facilitate Perineural Invasion of Pancreatic Cancer via HGF/c-Met Pathway
Pancreatic cancer (PC) is a highly lethal cancer that has a strong ability for invasion and metastasis, poor prognosis, and a stubbornly high death rate due to late diagnosis and early metastasis. Therefore, a better understanding of the mechanisms of metastasis should provide novel opportunities fo...
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Published in | Cell transplantation Vol. 28; no. 9-10; pp. 1289 - 1298 |
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Abstract | Pancreatic cancer (PC) is a highly lethal cancer that has a strong ability for invasion and metastasis, poor prognosis, and a stubbornly high death rate due to late diagnosis and early metastasis. Therefore, a better understanding of the mechanisms of metastasis should provide novel opportunities for therapeutic purposes. As a route of metastasis in PC, perineural invasion (PNI) occurs frequently; however, the molecular mechanism of PNI is still poorly understood. In this study, we show that the hepatocyte growth factor (HGF)/c-Met pathway plays a vital role in the PNI of PC. We found that HGF promotes PC cell migration and invasion by activating the HGF/c-Met pathway, and enhances the expression of nerve growth factor (NGF) and matrix metalloproteinase-9 (MMP9) in vitro. Furthermore, HGF significantly increased PC cell invasion of the dorsal root ganglia (DRG) and promoted the outgrowth of DRG in cocultured models of PC cells and DRG. In contrast, the capacity for invasion and the phenomenon of PNI in PC cells were reduced when the HGF/c-Met pathway was blocked by siRNA. In conclusion, PSCs facilitate PC cell PNI via the HGF/c-Met pathway. Targeting the HGF/c-Met signaling pathway could be a promising therapeutic strategy for PC. |
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AbstractList | Pancreatic cancer (PC) is a highly lethal cancer that has a strong ability for invasion and metastasis, poor prognosis, and a stubbornly high death rate due to late diagnosis and early metastasis. Therefore, a better understanding of the mechanisms of metastasis should provide novel opportunities for therapeutic purposes. As a route of metastasis in PC, perineural invasion (PNI) occurs frequently; however, the molecular mechanism of PNI is still poorly understood. In this study, we show that the hepatocyte growth factor (HGF)/c-Met pathway plays a vital role in the PNI of PC. We found that HGF promotes PC cell migration and invasion by activating the HGF/c-Met pathway, and enhances the expression of nerve growth factor (NGF) and matrix metalloproteinase-9 (MMP9) in vitro. Furthermore, HGF significantly increased PC cell invasion of the dorsal root ganglia (DRG) and promoted the outgrowth of DRG in cocultured models of PC cells and DRG. In contrast, the capacity for invasion and the phenomenon of PNI in PC cells were reduced when the HGF/c-Met pathway was blocked by siRNA. In conclusion, PSCs facilitate PC cell PNI via the HGF/c-Met pathway. Targeting the HGF/c-Met signaling pathway could be a promising therapeutic strategy for PC. Pancreatic cancer (PC) is a highly lethal cancer that has a strong ability for invasion and metastasis, poor prognosis, and a stubbornly high death rate due to late diagnosis and early metastasis. Therefore, a better understanding of the mechanisms of metastasis should provide novel opportunities for therapeutic purposes. As a route of metastasis in PC, perineural invasion (PNI) occurs frequently; however, the molecular mechanism of PNI is still poorly understood. In this study, we show that the hepatocyte growth factor (HGF)/c-Met pathway plays a vital role in the PNI of PC. We found that HGF promotes PC cell migration and invasion by activating the HGF/c-Met pathway, and enhances the expression of nerve growth factor (NGF) and matrix metalloproteinase-9 (MMP9) in vitro. Furthermore, HGF significantly increased PC cell invasion of the dorsal root ganglia (DRG) and promoted the outgrowth of DRG in cocultured models of PC cells and DRG. In contrast, the capacity for invasion and the phenomenon of PNI in PC cells were reduced when the HGF/c-Met pathway was blocked by siRNA. In conclusion, PSCs facilitate PC cell PNI via the HGF/c-Met pathway. Targeting the HGF/c-Met signaling pathway could be a promising therapeutic strategy for PC. |
Author | Nan, Ligang Ma, Qingyong Wu, Zheng Xiao, Ying Qin, Tao Wang, Zheng Li, Jie Ma, Jiguang Qian, Weikun |
AuthorAffiliation | 2 Emergency Department, People’s Hospital of Shaanxi Province, Xi’an, China 1 Department of Hepatobiliary Surgery, First Affiliated Hospital, Xi’an Jiaotong University, China Both the authors are co-first authors and contributed equally in this article 3 Department of Anesthesiology, First Affiliated Hospital, Xi’an Jiaotong University, China Both the authors are co-senior authors in this article |
AuthorAffiliation_xml | – name: 2 Emergency Department, People’s Hospital of Shaanxi Province, Xi’an, China – name: 3 Department of Anesthesiology, First Affiliated Hospital, Xi’an Jiaotong University, China – name: Both the authors are co-senior authors in this article – name: 1 Department of Hepatobiliary Surgery, First Affiliated Hospital, Xi’an Jiaotong University, China – name: Both the authors are co-first authors and contributed equally in this article |
Author_xml | – sequence: 1 givenname: Ligang orcidid: 0000-0002-4140-9158 surname: Nan fullname: Nan, Ligang – sequence: 2 givenname: Tao orcidid: 0000-0002-7674-698X surname: Qin fullname: Qin, Tao – sequence: 3 givenname: Ying surname: Xiao fullname: Xiao, Ying – sequence: 4 givenname: Weikun surname: Qian fullname: Qian, Weikun – sequence: 5 givenname: Jie surname: Li fullname: Li, Jie – sequence: 6 givenname: Zheng surname: Wang fullname: Wang, Zheng – sequence: 7 givenname: Jiguang surname: Ma fullname: Ma, Jiguang email: qyma56@mail.xjtu.edu.cn – sequence: 8 givenname: Qingyong surname: Ma fullname: Ma, Qingyong email: qyma56@mail.xjtu.edu.cn – sequence: 9 givenname: Zheng surname: Wu fullname: Wu, Zheng email: wuzheng@126.com |
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Keywords | perineural invasion pancreatic stellate cells pancreatic cancer HGF/c-Met pathway |
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Snippet | Pancreatic cancer (PC) is a highly lethal cancer that has a strong ability for invasion and metastasis, poor prognosis, and a stubbornly high death rate due to... Pancreatic cancer (PC) is a highly lethal cancer that has a strong ability for invasion and metastasis, poor prognosis, and a stubbornly high death rate due to... |
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SubjectTerms | c-Met protein Cell adhesion & migration Cell culture Cell migration Dorsal root ganglia Gelatinase B Growth factors Hepatocyte growth factor Matrix metalloproteinase Metalloproteinase Metastases Metastasis Nerve growth factor Original Pancreatic cancer Pheochromocytoma cells Signal transduction siRNA Stellate cells Therapeutic applications |
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Title | Pancreatic Stellate Cells Facilitate Perineural Invasion of Pancreatic Cancer via HGF/c-Met Pathway |
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