Abstract
Pancreatic cancer (PC), characterized by aggressive local invasion and metastasis, is one of the most malignant cancers. Gemcitabine is currently used as the standard drug for the treatment of advanced and metastatic PC, but with limited efficacy. In this study, we demonstrated that gemcitabine increased the expression of heparanase (HPA1), the only known mammalian endoglycosidase capable of cleaving heparan sulfate, both in vitro and in vivo. Furthermore, overexpression of HPA1 in PC cell lines enhanced proliferation and invasion, accompanied with elevated phosphorylation of EGFR. In addition, we showed that the NF-κB pathway mediated the gemcitabine-induced HPA1 expression. Importantly, we found that an HPA1 inhibitor attenuated gemcitabine-induced invasion of PC cells. Finally, we showed that HPA1 was of negative prognostic value for PC patients. Taken together, our results demonstrated that gemcitabine-induced HPA1 promotes proliferation and invasion of PC cells through activating EGFR, implying that HPA1 may serve as promising therapeutic target in the treatment of PC.
Highlights
Pancreatic cancer (PC) is the fourth leading cause of cancer related death in the USA with an extremely low 5-year survival of less than 5% [1]
Our results demonstrated that gemcitabine-induced HPA1 promotes proliferation and invasion of PC cells through activating EGFR, implying that HPA1 may serve as promising therapeutic target in the treatment of PC
As HPA1 plays versatile roles in tumor progression, we examined the change of HPA1 expression in gemcitabine treated PC cells
Summary
Pancreatic cancer (PC) is the fourth leading cause of cancer related death in the USA with an extremely low 5-year survival of less than 5% [1]. Surgical resection at present offers the only chance for cure. More than 80% of PC cases are identified as unresectable at diagnosis, due to metastatic or locally advanced tumors, and are subjected to chemotherapy [2]. Gemcitabine has been the standard treatment for advanced and metastatic PC patients [3]. Most PC patients do not respond well to gemcitabine treatment, and those who do respond may develop chemoresistance and subsequent disease progression [4]. There is an urgent need to understand the biological mechanisms of disease progression following gemcitabine treatment to improve the prognosis of PC patients
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
