C5 alpha secreted by tumor mesenchymal stem-like cells mediates resistance to 5-aminolevulinic acid-based photodynamic therapy against glioblastoma tumorspheres
- Authors
- Park, Junseong; Oh, Seung Jae; Shim, Jin-Kyoung; Ji, Young Bin; Moon, Ju Hyung; Kim, Eui Hyun; Huh, Yong-Min; Suh, Jin-Suck; Chang, Jong Hee; Lee, Su-Jae; Kang, Seok-Gu
- Issue Date
- Jul-2023
- Publisher
- SPRINGER
- Keywords
- 5-Aminolevulilic acid; Acquired PDT resistance; Glioblastoma; Photodynamic diagnosis; Photodynamic therapy; Tumor mesenchymal stem-like cells
- Citation
- JOURNAL OF CANCER RESEARCH AND CLINICAL ONCOLOGY, v.149, no.8, pp.4391 - 4402
- Indexed
- SCIE
SCOPUS
- Journal Title
- JOURNAL OF CANCER RESEARCH AND CLINICAL ONCOLOGY
- Volume
- 149
- Number
- 8
- Start Page
- 4391
- End Page
- 4402
- URI
- https://scholarworks.bwise.kr/hanyang/handle/2021.sw.hanyang/190535
- DOI
- 10.1007/s00432-022-04347-w
- ISSN
- 0171-5216
- Abstract
- Purpose Advancements in photodynamic diagnosis (PDD) and photodynamic therapy (PDT) as a standard care in cancer therapy have been limited. This study is aimed to investigate the clinical availability of 5-aminolevulinic acid (5-ALA)-based PDD and PDT in glioblastoma (GBM) patient-derived tumorspheres (TSs) and mouse orthotopic xenograft model. Methods PDT was performed using a 635 nm light-emitting diode (LED). Transcriptome profiles were obtained from microarray data. For knockdown of C5 alpha, siRNA was transfected into tumor mesenchymal stem-like cells (tMSLCs). The invasiveness of TSs was quantified using collagen-based 3D invasion assays. Results Treatment with 1 mM 5 ALA induced distinct protoporphyrin IX (PpIX) fluorescence in GBM TSs, but not in non-tumor cells or tissues, including tMSLCs. These observations were negatively correlated with the expression levels of FECH, which catalyzes the conversion of accumulated PpIX to heme. Furthermore, the 5-ALA-treated GBM TSs were sensitive to PDT, thereby significantly decreasing cell viability and invasiveness. Notably, the effects of PDT were abolished by culturing TSs with tMSLC-conditioned media. Transcriptome analysis revealed diverse tMSLC-secreted chemokines, including C5 alpha, and their correlations with the expression of stemness- or mesenchymal transition-associated genes. By adding or inhibiting C5 alpha, we confirmed that acquired resistance to PDT was induced via tMSLC-secreted C5 alpha. Conclusions Our results show substantial therapeutic effects of 5-ALA-based PDT on GBM TSs, suggesting C5 alpha as a key molecule responsible for PDT resistance. These findings could trigger PDT as a standard clinical modality for the treatment of GBM.
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