Recapitulation of Hypoxic Tumor –stroma Microenvironment to Study Photodynamic Therapy Implications

In this study, we demonstrated the consequences of a hypoxic stromal phenotype on tumor mass for exploring PDT response. We mimicked TME complexity implementing colon cancer cells and fibroblasts 3D cultures called spheroids. Using hypoxia reporting lines, we verified that homotypic spheroids exhibited a size ‐dependent transcriptional HIF‐1 activity. When cocultured, fibroblasts were localized in the hypoxic core. In homotypic stromal spheroids, the distribution of the endogenous photosensitizer PpIX was homogeneous while decreased in hypoxic areas of tumor 3D cultures. When monocultured, fibroblast s were more efficient to produce PpIX from its prodrug Me‐ALA. Interestingly, the cross talk between cancer cells and fibroblasts attenuated PpIX accumulation and conferred tumor PDT resistance when compared to homotypic 3D cultures. Overall, our data suggest that stroma and tumor act in an integr ated, reciprocal fashion which could ultimately influence on therapeutic response.
Source: Photochemistry and Photobiology - Category: Science Authors: Tags: Research Article Source Type: research