Photodestruction of Stromal Fibroblasts Enhances Tumor Response to PDT in 3D Pancreatic Cancer Coculture Models
Vida Karimniaa b, Imran Rizvic d e f g h, Frank John Slacki j, Jonathan P. Cellia b✉
- aDepartment of Physics University of Massachusetts at Boston Boston MA USA
- bDepartment of Physics, University of Massachusetts at Boston, Boston, MA, USA
- cJoint Department of Biomedical Engineering University of North Carolina at Chapel Hill Chapel Hill NC USA
- dLineberger Comprehensive Cancer Center University of North Carolina School of Medicine Chapel Hill NC USA
- eNorth Carolina State University Raleigh NC USA
- fJoint Department of Biomedical Engineering, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA
- gLineberger Comprehensive Cancer Center, University of North Carolina School of Medicine, Chapel Hill, NC, USA
- hNorth Carolina State University, Raleigh, NC, USA
- iDepartment of Pathology BIDMC Cancer Center/Harvard Medical School Boston MA USA
- jDepartment of Pathology, BIDMC Cancer Center/Harvard Medical School, Boston, MA, USA
- ✉Corresponding author
Papers open inside SciRah from the original publisher or repository; SciRah never hosts them.
Abstract
Pancreatic ductal adenocarcinoma (PDAC) is among the most lethal of human cancers. The dismal response of PDAC to virtually all therapeutics is associated, in part, with a characteristically dense fibrotic stroma. This stroma not only acts as a barrier to drug perfusion, but also promotes tumor survival through paracrine crosstalk and biophysical interactions. Photodynamic therapy (PDT) is being explored for PDAC treatment, though the impact of tumor-promoting stromal crosstalk on PDT response in PDAC is not well-characterized. The current study assesses the effect of tumor-stroma interactions on response to PDT or chemotherapy in heterocellular 3D cocultures using PDAC cells and two different fibroblastic cell types (pancreatic stellate cells, PSCs, and a normal human fibroblast cell line, MRC5) embedded in extracellular matrix (ECM). While stromal fibroblasts promote resistance to chemotherapy as expected, PDAC 3D nodules in coculture with fibroblasts exhibit increased response to PDT relative to homotypic cultures. These results point to the potential for PDT to overcome tumor-promoting stromal interactions associated with poor therapeutic response in PDAC.
TL;DRThe results point to the potential for PDT to overcome tumor‐promoting stromal interactions associated with poor therapeutic response in PDAC, and increase response to PDT relative to homotypic cultures. (Semantic Scholar)