Panoply™ Human NTSR1 Over-expressing Stable Cell Line

Pancreatic cancer is one of the cancers with the worst prognosis, with a 5-year survival rate of approximately 5%–10%. Therefore, there is an urgent need to identify molecular targets for the treatment of pancreatic cancer. Based on previous RNA sequencing analysis, researchers found that the expression level of neurotensin receptor 1 (NTSR1) was elevated in highly malignant pancreatic cancer cell lines. Furthermore, re-analysis of clinical databases showed that NTSR1 expression levels are elevated in advanced pancreatic cancer, and high NTSR1 levels are associated with poor prognosis. Overexpression of NTSR1 in human pancreatic cancer cells Panc-1 and SUIT-2 accelerated their tumorigenic and metastatic capabilities in vivo. In addition, RNA sequencing analysis revealed that neurotensin (NTS) stimulation activates the MAPK and NF-κB signaling pathways in highly malignant pancreatic cancer cell lines and uncovered many novel target genes of NTS in pancreatic cancer cells. NTS stimulation increased the expression of MMP-9 and other pro-inflammatory cytokines and chemokines in pancreatic cancer cells. Moreover, treatment with the selective NTSR1 antagonist SR48692 inhibited the activation of MAPK and NF-κB signaling pathways and the induction of target genes in pancreatic cancer cells in vitro, while administration of SR48692 attenuated the tumorigenicity of pancreatic cancer cells in vivo. These findings suggest that NTSR1 may be a prognostic marker and a molecular target for the treatment of pancreatic cancer.

The functional role of NTSR1 in pancreatic cancer progression was examined in vivo using NTSR1-overexpressing cells. Due to the low expression levels of NTSR1 in parental Panc-1 and SUIT-2 cells, researchers constructed NTSR1-overexpressing Panc-1 and SUIT-2 cells (Figure 1A). In vitro experiments showed no significant difference in proliferative capacity between NTSR1-overexpressing cells and control cells. However, when researchers orthotopically transplanted NTSR1-overexpressing cells into the pancreas of nude mice, they found that NTSR1 significantly promoted the formation of primary tumors in SUIT-2 cells and partially promoted the formation of primary tumors in Panc-1 cells (Figure 1B). By observing metastatic lesions in the lungs and liver using ex vivo bioluminescence imaging, researchers found an increased incidence of lung metastasis in mice carrying NTSR1-overexpressing cells (Figure 1C). These results indicate that the NTSR1-mediated signaling pathway plays a pro-tumorigenic role in pancreatic cancer.

Figure 1. Overexpression of NTSR1 promotes tumorigenicity and metastasis of pancreatic cancer cells. (Takahashi K, et al., 2021)