title: Pleiotrophin promotes perineural invasion in pancreatic cancer.
abstract: Perineural invasion (PNI) in pancreatic cancer is an important cause of local recurrence, but little is known about its mechanism. Pleiotrophin (PTN) is an important neurotrophic factor. It is of interest that our recent experimental data showed its involvement in PNI of pancreatic cancer. PTN strongly presents in the cytoplasm of pancreatic cancer cells, and high expression of PTN and its receptor may contribute to the high PNI of pancreatic cancer. Correspondingly, PNI is prone to happen in PTN-positive tumors. We thus hypothesize that, as a neurite growth-promoting factor, PTN may promote PNI in pancreatic cancer. PTN is released at the time of tumor cell necrosis, and binds with its high-affinity receptor, N-syndecan on pancreatic nerves, to promote neural growth in pancreatic cancer. Furthermore, neural destruction leads to a distorted neural homeostasis. Neurons and Schwann cells produce more N-syndecan in an effort to repair the pancreatic nerves. However, the abundance of N-syndecan attracts further PTN-positive cancer cells to the site of injury, creating a vicious cycle. Ultimately, increased PTN and N-syndecan levels, due to the continuous nerve injury, may promote cancer invasion and propagation along the neural structures. Therefore, it is meaningful to discuss the relationship between PTN/N-syndecan signaling and PNI in pancreatic cancer, which may lead to a better understanding of the mechanism of PNI in pancreatic cancer.
authors.affiliation: Jun Yao, Xiu-Feng Hu, Xiao-Shan Feng, She-Gan Gao, Department of Oncology, the First Affiliated Hospital of Henan University of Science and Technology, Luoyang 471003, Henan Province, China.
authors.forename: Jun
authors.initials: J
authors.lastname: Yao
authors.forename: Xiu-Feng
authors.initials: XF
authors.lastname: Hu
authors.forename: Xiao-Shan
authors.initials: XS
authors.lastname: Feng
authors.forename: She-Gan
authors.initials: SG
authors.lastname: Gao
mesh_terms: D000818:Animals; D014408:Biomarkers, Tumor / Q000378:metabolism*; D002352:Carrier Proteins / Q000378:metabolism*; D002465:Cell Movement; D016207:Cytokines / Q000378:metabolism*; D006801:Humans; D008024:Ligands; D009361:Neoplasm Invasiveness; D009474:Neurons / Q000378:metabolism* / Q000473:pathology; D010190:Pancreatic Neoplasms / Q000378:metabolism* / Q000473:pathology / Q000628:therapy; D011379:Prognosis; D015398:Signal Transduction; D053670:Syndecan-3 / Q000378:metabolism
chemical_list: D014408:Biomarkers, Tumor; D002352:Carrier Proteins; D016207:Cytokines; D008024:Ligands; D053670:Syndecan-3; C066845:pleiotrophin
keywords: N-syndecan; Neurite outgrowth; Pancreatic cancer; Perineural invasion; Pleiotrophin