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

Area of Science:

• Oncology
• Biomedical Engineering
• Cancer Research

Background:

• The tumor microenvironment (TME) involves fibroblasts supporting tumor growth and therapeutic resistance.
• The specific impact of fibroblasts on photodynamic therapy (PDT) outcomes remains unclear.
• PDT relies on light, oxygen, and photosensitizers to induce cell death.

Purpose of the Study:

• To investigate the role of fibroblasts and hypoxia in the TME on PDT response.
• To explore how cancer cell-fibroblast interactions influence photosensitizer distribution and PDT efficacy.

Main Methods:

• Utilized 3D co-culture spheroids of colon cancer cells and fibroblasts to mimic TME complexity.
• Employed hypoxia reporting lines to assess HIF-1 activity.
• Quantified endogenous photosensitizer (PpIX) distribution and production.

Main Results:

• Fibroblasts localized to the hypoxic core in co-cultured spheroids.
• Hypoxia decreased photosensitizer accumulation in tumor spheroids.
• Cancer cell-fibroblast crosstalk reduced photosensitizer levels and increased PDT resistance compared to single-culture spheroids.

Conclusions:

• Tumor-stroma interactions are reciprocal and influence therapeutic response.
• Fibroblast-mediated hypoxia and crosstalk can impair PDT efficacy.
• Understanding these interactions is crucial for optimizing PDT strategies.