Photo ‐destruction of Stromal Fibroblasts Enhances Tumor Response to PDT in 3D Pancreatic Cancer Co‐culture Models

AbstractPancreatic 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 acts not only 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 co‐cultures 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 co‐culture with fibroblasts exhibit increased response to PDT relative to homotypic cultures. These resu lts point to the potential for PDT to overcome tumor‐promoting stromal interactions associated with poor therapeutic response in PDAC.

Source: Photochemistry and Photobiology - October 3, 2020 Category: Science Authors: Vida Karimnia, Imran Rizvi, Frank J. Slack, Jonathan P. Celli Tags: RESEARCH ARTICLE Source Type: research