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.