Photodynamic therapy remodels the prostate cancer microenvironment by suppressing cancer-associated fibroblast-mediated calcium signaling.
[BACKGROUND] Prostate cancer (PCa) remains a leading cause of cancer burden in men worldwide.
APA
Zhao D, Xi Y, et al. (2026). Photodynamic therapy remodels the prostate cancer microenvironment by suppressing cancer-associated fibroblast-mediated calcium signaling.. Journal of photochemistry and photobiology. B, Biology, 279, 113440. https://doi.org/10.1016/j.jphotobiol.2026.113440
MLA
Zhao D, et al.. "Photodynamic therapy remodels the prostate cancer microenvironment by suppressing cancer-associated fibroblast-mediated calcium signaling.." Journal of photochemistry and photobiology. B, Biology, vol. 279, 2026, pp. 113440.
PMID
42024997
Abstract
[BACKGROUND] Prostate cancer (PCa) remains a leading cause of cancer burden in men worldwide. Photodynamic therapy (PDT) offers a minimally invasive therapeutic option, but the molecular mechanisms underlying its anti-tumor efficacy, particularly in the context of the tumor microenvironment, are not fully elucidated.
[METHODS] Integrated bioinformatics analyses of bulk and single-cell transcriptomic datasets identified key PDT-responsive molecular pathways and cell populations in PCa. Functional enrichment and intercellular communication analyses were performed to investigate tumor-stroma cell interactions. The efficacy and mechanism of PDT were further validated using in vitro co-culture systems and in vivo xenograft models, with a focus on calcium signaling, CAF activation, and RGS2 regulation.
[RESULTS] Transcriptomic analyses revealed significant enrichment of cancer-associated fibroblast (CAF)-related processes both in PCa progression and following PDT. CAFs promoted early epithelial malignancy via IGF1-IGF1R signaling, which was coupled to increased calcium influx in tumor cells. PDT disrupted this pro-tumorigenic axis, leading to suppressed CAF activation, reduced tumor cell viability, and a marked reduction of intracellular calcium levels. Eleven candidate PDT-responsive genes were identified, with RGS2 prioritized as a key protective factor modulating calcium signaling and tumor-stroma interactions. PDT upregulated RGS2 in both tumor and stromal compartments while downregulating calcium channel proteins.
[CONCLUSION] PDT enhances therapeutic efficacy in PCa not only through direct tumor cell cytotoxicity, but also via reprogramming of the tumor microenvironment, primarily by disrupting the CAF-mediated IGF1/IGF1R‑calcium signaling axis and upregulating RGS2. Targeting this pathway may hold promise for developing more effective, personalized PDT-based therapeutic strategies in PCa.
[METHODS] Integrated bioinformatics analyses of bulk and single-cell transcriptomic datasets identified key PDT-responsive molecular pathways and cell populations in PCa. Functional enrichment and intercellular communication analyses were performed to investigate tumor-stroma cell interactions. The efficacy and mechanism of PDT were further validated using in vitro co-culture systems and in vivo xenograft models, with a focus on calcium signaling, CAF activation, and RGS2 regulation.
[RESULTS] Transcriptomic analyses revealed significant enrichment of cancer-associated fibroblast (CAF)-related processes both in PCa progression and following PDT. CAFs promoted early epithelial malignancy via IGF1-IGF1R signaling, which was coupled to increased calcium influx in tumor cells. PDT disrupted this pro-tumorigenic axis, leading to suppressed CAF activation, reduced tumor cell viability, and a marked reduction of intracellular calcium levels. Eleven candidate PDT-responsive genes were identified, with RGS2 prioritized as a key protective factor modulating calcium signaling and tumor-stroma interactions. PDT upregulated RGS2 in both tumor and stromal compartments while downregulating calcium channel proteins.
[CONCLUSION] PDT enhances therapeutic efficacy in PCa not only through direct tumor cell cytotoxicity, but also via reprogramming of the tumor microenvironment, primarily by disrupting the CAF-mediated IGF1/IGF1R‑calcium signaling axis and upregulating RGS2. Targeting this pathway may hold promise for developing more effective, personalized PDT-based therapeutic strategies in PCa.
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