Protein 4.1R affects photodynamic therapy for B16 melanoma by regulating the transport of 5-aminolevulinic acid
Bowen Li1, Xiaolin Zhang2, Yu Lu1
1Henan Institute of Medical and Pharmaceutical Sciences, Academy of Medical Science, Zhengzhou University, Zhengzhou, 450052, Henan, China.
Abstract:
Melanoma is the most aggressive malignant tumor of skin cancer as it can grow rapidly and metastasize. Photodynamic therapy (PDT) is a promising cancer ablation method for skin tumors, although it lacks efficiency owing to factors such as tumor characteristics, delivery of photosensitizers, immune response in vivo etc. Extensive investigation of molecules that can potentially modulate treatment efficacy is required. Protein 4.1R is a cytoskeletal protein molecule. Previous studies have shown that protein 4.1R knockdown reduces PDT sensitivity in mouse embryonic fibroblast cells. However, the functional role of protein 4.1R in melanoma is unclear. In this study, we aimed to elucidate the effect of protein 4.1R on PDT for melanoma in mice and the mechanism of anti-tumor immunity. Our results indicated that CRISPR/Cas9-mediated protein 4.1R knockout promotes the proliferation, migration, and invasion of B16 cells. We further investigated the potential mechanism of protein 4.1R on tumor cell PDT sensitivity. Our results showed that protein 4.1R knockout reduced the expression of membrane transporters γ-aminobutyric acid transporter (GAT)-1 and (GAT)-2 in B16 cells, which affected 5-ALA transmembrane transport and reduced the efficiency of PDT on B16 cells. Protein 4.1R knockout downregulated the anti-tumor immune response triggered by PDT in vivo. In conclusion, our data suggest that protein 4.1R is an important regulator in PDT for tumors and may promote the progress and efficacy of melanoma treatment.
Insights
Protein 4.1R enhances photodynamic therapy (PDT) efficacy for melanoma. Its absence increases tumor cell growth and reduces PDT effectiveness by impacting transporter expression and anti-tumor immunity.
Area of Science:
- Oncology
- Immunology
- Molecular Biology
Background:
- Melanoma is an aggressive skin cancer with metastatic potential.
- Photodynamic therapy (PDT) shows promise for skin tumors but faces efficiency challenges.
- The role of Protein 4.1R in melanoma PDT efficacy and anti-tumor immunity is not well understood.
Purpose of the Study:
- To investigate the effect of Protein 4.1R on melanoma PDT in mice.
- To elucidate the underlying mechanisms of anti-tumor immunity modulation.
- To determine Protein 4.1R's role in melanoma progression and treatment response.
Main Methods:
- Utilized CRISPR/Cas9 technology for Protein 4.1R knockout in B16 melanoma cells.
- Assessed cell proliferation, migration, and invasion.
- Quantified expression of γ-aminobutyric acid transporters (GAT-1 and GAT-2).
- Evaluated in vivo anti-tumor immune response post-PDT.
Main Results:
- Protein 4.1R knockout promoted B16 cell proliferation, migration, and invasion.
- Knockout reduced GAT-1 and GAT-2 expression, impairing 5-aminolevulinic acid (5-ALA) transport and PDT efficiency.
- Protein 4.1R deficiency downregulated PDT-induced anti-tumor immunity in vivo.
Conclusions:
- Protein 4.1R is a critical regulator of PDT efficacy in melanoma.
- Loss of Protein 4.1R negatively impacts melanoma cell behavior and reduces PDT effectiveness.
- Protein 4.1R plays a significant role in modulating the anti-tumor immune response during PDT.
