In a study published by Gao et al in The American Journal of Pathology, scientists reported the discovery of an increased level of the neuroprotein sortilin in pancreatic cancer cells. The investigators speculated that this finding may lead to the development of more effective treatment for patients with pancreatic cancer.
“There is currently no good therapy for pancreatic cancer,” explained lead investigator Hubert Hondermarck, PhD, of the School of Biomedical Sciences and Pharmacy and Hunter Medical Research Institute at the University of Newcastle, Australia. “What we need is a targeted therapy that could slow down the rapid progression of the disease, to allow more time for chemotherapy and radiotherapy to be more effective.”
The neuronal membrane protein sortilin is emerging as a key player in the regulation of neuronal viability and function, and there are indications that it is involved in the deregulation of cancer cell viability. Sortilin is overexpressed in breast, lung, and thyroid cancers; it can promote cancer cell invasion in glioblastoma; and it participates in cancer cell adhesion and metastasis in colorectal cancer. However, its expression and impact in pancreatic cancer was not previously known.
Study Methods
In this study, investigators examined several pancreatic cancer cell lines alongside pancreatic ductal epithelial cells and established that sortilin expression levels were higher in the cancer cells, as demonstrated by Western blot and mass spectrometry. The increased sortilin level in pancreatic cancer cells was confirmed by immunohistochemistry in a series of 99 human pancreatic adenocarcinomas compared to 48 normal pancreatic tissues.
Furthermore, sortilin was found to contribute to pancreatic cancer invasion in vitro through potentially maintaining the focal adhesion kinase (FAK) signaling pathway. Researchers also found that sortilin levels were higher in women with pancreatic cancer vs men with the malignancy.
“Our finding of higher sortilin expression in female patients suggests a possible regulation of sortilin gene expression by estrogen receptors, but further functional analyses are needed to confirm this hypothesis,” noted Dr. Hondermarck.
The main issue with pancreatic cancer is the local invasiveness of the tumor that leads to the destruction of the pancreas, rapidly causing death. This study showed that inhibiting sortilin with specific drugs or immunotherapy leads to a strong decrease in pancreatic cancer cell invasiveness. Therefore, specifically targeting sortilin is likely to complement and improve the efficacy of existing treatments. However, no statistically significant association was found between sortilin expression and pancreatic cancer aggressiveness. Therefore, although sortilin contributes to pancreatic cancer cell invasion, it is likely not the only factor involved.
“Together, these data reveal that sortilin contributes to pancreatic cancer invasion and is a potential therapeutic target,” concluded Dr. Hondermarck. “This discovery may lead to the development of more efficient treatment against the disease.”
Disclosure: The study authors reported no conflicts of interest.
