Glutamine-Mediated Tumor-Stromal Interaction: A Novel Target for Pancreatic Cancer Treatment
Abstract
Pancreatic ductal adenocarcinoma (PDAC) is a devastating disease with appallingly poor outcome. Recent years have witnessed the development of a number of combination therapies that have produced modest survival improvement but at the cost of increased adverse effects. We have recently demonstrated that pancreatic stellate cells (PSCs) secretes glutamine (Q) to promote the growth of pancreatic cancer cells (PCCs). I have also identified increased protein levels of pSTAT3 and survivin under conditions of Q-stimulation. Notably, Q-stimulated proliferation and pSTAT3 were attenuated by a novel compound called palmatine (PMT). Since both STAT3 and survivins involved in therapeutic resistance to Gemcitabine (GEM) and Abraxane (Abr)in PDAC, we tested the hypothesis that Q-mediated signaling promotes PSC-PCC communication causes increased survival hallmarks of PDAC cells and that PMT can disrupt this communication to potentiate response to conventional therapeutics. Our results indicated that (i) PMT attenuated Q-mediated enhanced proliferation, clonogenicity and anchorage independent growth ability in multiple PDAC cell lines; (ii) PMT inhibits Q-mediated increased proliferation partially through STAT3; (iii) PMT reduces Q-induced increased Survivins promoter activity through STAT3 and (iv) PMT works synergistically with GEM and Abr in different cell lines. Taken together, these data show potential clinical utility for the combination of PMT plus GEM in the treatment of pancreatic cancer.
Document Details
- Document Type
- Technical Report
- Publication Date
- Sep 01, 2020
- Accession Number
- AD1117699
Entities
People
- Xiaoyu Yang
Organizations
- University of Texas Health Science Center at San Antonio