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Photodestruction of Stromal Fibroblasts Enhances Tumor Response to PDT in 3D Pancreatic Cancer Coculture Models
Author(s) -
Karimnia Vida,
Rizvi Imran,
Slack Frank J.,
Celli Jonathan P.
Publication year - 2020
Publication title -
photochemistry and photobiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.818
H-Index - 131
eISSN - 1751-1097
pISSN - 0031-8655
DOI - 10.1111/php.13339
Subject(s) - stromal cell , stroma , cancer research , pancreatic cancer , extracellular matrix , paracrine signalling , cancer associated fibroblasts , crosstalk , photodynamic therapy , tumor microenvironment , desmoplasia , fibroblast , cell culture , pathology , chemistry , medicine , biology , cancer , microbiology and biotechnology , tumor cells , immunohistochemistry , receptor , physics , genetics , organic chemistry , optics
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.