Stellate Cells Aid Growth-Permissive Metabolic Reprogramming and Promote Gemcitabine Chemoresistance in Pancreatic Cancer
Department of Pharmacology, Institute of Clinical Medicine, University of Oslo, 0316 Oslo, Norway
Department of Hepato-Pancreato-Biliary Surgery, Institute of Clinical Medicine, University of Oslo, 0318 Oslo, Norway
Department of Hepato-Pancreato-Biliary Surgery, Oslo University Hospital Rikshospitalet, 0424 Oslo, Norway
Author to whom correspondence should be addressed.
Academic Editor: Hidekazu Suzuki
Received: 15 December 2020
Revised: 4 January 2021
Accepted: 29 January 2021
Published: 3 February 2021
The great majority, more than 90%, of patients with pancreatic ductal adenocarcinoma (PDAC) die within less than five years after detection of the disease, despite recent treatment advances. The poor prognosis is related to late diagnosis, aggressive disease progression, and tumor resistance to conventional chemotherapy. PDAC tumor tissue is characterized by dense fibrosis and poor nutrient availability. A large portion of the tumor is made up of stromal fibroblasts, the pancreatic stellate cells (PSCs), which are known to contribute to tumor progression in several ways. PSCs have been shown to act as an alternate energy source, induce drug resistance, and inhibit drug availability in tumor cells, however, the underlying exact molecular mechanisms remain unknown. In this literature review, we discuss recent available knowledge about the contributions of PSCs to the overall progression of PDAC via changes in tumor metabolism and how this is linked to therapy resistance.