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Published on: January 5, 2024
ALA-PDT results in phenotypic changes and decreased cellular invasion in surviving cancer cells
Tsuimin Tsai1, Hong Tai Ji, Pei-Chi Chiang
1Graduate Institute of Biomedical Materials and Engineering, Graduate School of Dentistry, Taipei Medical University, Taipei 110, Taiwan.
Background And Objectives:
The mechanisms of photodynamic therapy (PDT) have been studied on the cellular and tissue levels. However, the cellular behaviors of cancer cells survived from PDT are still not clear. This study attempted to investigate the influence of 5-aminolevulinic acid (ALA)-based PDT on the invasion ability as well as molecular changes in surviving cancer cells and their progeny.
Materials And Methods:
The systematic effects of ALA-PDT were evaluated using human invasive carcinoma cells (lung adenocarcinoma CL1-5 cells, melanoma A375 cells and breast carcinoma MDA-MB-231 cells). To study the cellular behaviors of surviving cancer cells, PDT-derived variants were established as stable cell lines after consecutive treatment with ALA-PDT. Scratch wound assay and invasion assay were performed to evaluate the migration and invasion ability in the surviving cancer cells and the established PDT-derived variants. RT-PCR and immunoblot analysis were performed to examine the expression levels of epidermal growth factor receptor (EGFR).
Results:
Though ALA-PDT caused differential phototoxicity among these invasive carcinoma cells, reduced migration was found in all the surviving cancer cells Compared to parental cancer cells, the established PDT-derived variants exerted significant phenotypic changes of cellular morphology, reduced mitochondrial function and a suppressed cellular invasiveness. Furthermore, correlated with the reduced invasion ability, expression of EGFR was downregulated in these established PDT-derived variants.
Conclusions:
Except for direct cell killing, ALA-PDT could reduce EGFR expression and invasion ability of the surviving cancer cells and these effects could further pass to the progeny. The results from this study provide insights into a new mechanism by which PDT might affect cellular behaviors and tumor metastasis.
Insights
Photodynamic therapy using 5-aminolevulinic acid (ALA-PDT) reduces cancer cell invasion and epidermal growth factor receptor (EGFR) expression. These anti-metastatic effects in surviving cancer cells can be passed to their progeny.
Area of Science:
- Oncology
- Cell Biology
- Photochemistry
Background:
- Photodynamic therapy (PDT) mechanisms are understood at cellular and tissue levels.
- The behavior of cancer cells surviving PDT remains unclear.
- Investigating post-PDT cellular changes is crucial for understanding treatment efficacy and metastasis.
Purpose of the Study:
- To investigate the impact of 5-aminolevulinic acid-based photodynamic therapy (ALA-PDT) on the invasion capabilities of surviving cancer cells.
- To analyze molecular alterations, specifically epidermal growth factor receptor (EGFR) expression, in cancer cells post-ALA-PDT.
- To determine if these acquired traits are heritable by the progeny of surviving cancer cells.
Main Methods:
- Human invasive carcinoma cell lines (lung, melanoma, breast) were subjected to ALA-PDT.
- Surviving cells were cultured to establish PDT-derived variants.
- Migration and invasion assays were performed.
- Gene and protein expression of EGFR were analyzed using RT-PCR and immunoblotting.
Main Results:
- ALA-PDT induced reduced migration in all surviving cancer cell types.
- PDT-derived variants exhibited altered morphology, reduced mitochondrial function, and suppressed invasiveness compared to parental cells.
- EGFR expression was downregulated in PDT-derived variants, correlating with reduced invasion.
Conclusions:
- ALA-PDT not only kills cancer cells but also reduces their invasion potential and EGFR expression.
- These anti-metastatic effects are heritable, passing to the progeny of surviving cells.
- ALA-PDT presents a novel mechanism to potentially inhibit tumor metastasis.
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