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C5 alpha secreted by tumor mesenchymal stem-like cells mediates resistance to 5-aminolevulinic acid-based photodynamic therapy against glioblastoma tumorspheres

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dc.contributor.author강석구-
dc.contributor.author김의현-
dc.contributor.author문주형-
dc.contributor.author박준성-
dc.contributor.author서진석-
dc.contributor.author오승재-
dc.contributor.author장종희-
dc.contributor.author지영빈-
dc.contributor.author허용민-
dc.date.accessioned2024-05-30T06:59:25Z-
dc.date.available2024-05-30T06:59:25Z-
dc.date.issued2023-07-
dc.identifier.issn0171-5216-
dc.identifier.urihttps://ir.ymlib.yonsei.ac.kr/handle/22282913/199502-
dc.description.abstractPurpose 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.-
dc.description.statementOfResponsibilityrestriction-
dc.languageEnglish, German-
dc.publisherSpringer-Verlag-
dc.relation.isPartOfJOURNAL OF CANCER RESEARCH AND CLINICAL ONCOLOGY-
dc.rightsCC BY-NC-ND 2.0 KR-
dc.subject.MESHAminolevulinic Acid / pharmacology-
dc.subject.MESHAminolevulinic Acid / therapeutic use-
dc.subject.MESHAnimals-
dc.subject.MESHCell Line, Tumor-
dc.subject.MESHGlioblastoma* / drug therapy-
dc.subject.MESHGlioblastoma* / genetics-
dc.subject.MESHGlioblastoma* / pathology-
dc.subject.MESHHumans-
dc.subject.MESHMice-
dc.subject.MESHPhotochemotherapy* / methods-
dc.subject.MESHPhotosensitizing Agents / pharmacology-
dc.subject.MESHPhotosensitizing Agents / therapeutic use-
dc.subject.MESHProtoporphyrins / metabolism-
dc.subject.MESHProtoporphyrins / pharmacology-
dc.titleC5 alpha secreted by tumor mesenchymal stem-like cells mediates resistance to 5-aminolevulinic acid-based photodynamic therapy against glioblastoma tumorspheres-
dc.typeArticle-
dc.contributor.collegeCollege of Medicine (의과대학)-
dc.contributor.departmentDept. of Neurosurgery (신경외과학교실)-
dc.contributor.googleauthorJunseong Park-
dc.contributor.googleauthorSeung Jae Oh-
dc.contributor.googleauthorJin-Kyoung Shim-
dc.contributor.googleauthorYoung Bin Ji-
dc.contributor.googleauthorJu Hyung Moon-
dc.contributor.googleauthorEui Hyun Kim-
dc.contributor.googleauthorYong-Min Huh-
dc.contributor.googleauthorJin-Suck Suh-
dc.contributor.googleauthorJong Hee Chang-
dc.contributor.googleauthorSu-Jae Lee-
dc.contributor.googleauthorSeok-Gu Kang-
dc.identifier.doi10.1007/s00432-022-04347-w-
dc.contributor.localIdA00036-
dc.contributor.localIdA00837-
dc.contributor.localIdA01383-
dc.contributor.localIdA05830-
dc.contributor.localIdA01916-
dc.contributor.localIdA02383-
dc.contributor.localIdA03470-
dc.contributor.localIdA04687-
dc.contributor.localIdA04359-
dc.relation.journalcodeJ01283-
dc.identifier.eissn1432-1335-
dc.identifier.pmid36107247-
dc.identifier.urlhttps://link.springer.com/article/10.1007/s00432-022-04347-w-
dc.subject.keyword5-Aminolevulilic acid-
dc.subject.keywordAcquired PDT resistance-
dc.subject.keywordGlioblastoma-
dc.subject.keywordPhotodynamic diagnosis-
dc.subject.keywordPhotodynamic therapy-
dc.subject.keywordTumor mesenchymal stem-like cells-
dc.contributor.alternativeNameKang, Seok Gu-
dc.contributor.affiliatedAuthor강석구-
dc.contributor.affiliatedAuthor김의현-
dc.contributor.affiliatedAuthor문주형-
dc.contributor.affiliatedAuthor박준성-
dc.contributor.affiliatedAuthor서진석-
dc.contributor.affiliatedAuthor오승재-
dc.contributor.affiliatedAuthor장종희-
dc.contributor.affiliatedAuthor지영빈-
dc.contributor.affiliatedAuthor허용민-
dc.citation.volume149-
dc.citation.number8-
dc.citation.startPage4391-
dc.citation.endPage4402-
dc.identifier.bibliographicCitationJOURNAL OF CANCER RESEARCH AND CLINICAL ONCOLOGY, Vol.149(8) : 4391-4402, 2023-07-
Appears in Collections:
1. College of Medicine (의과대학) > Research Institute (부설연구소) > 1. Journal Papers
1. College of Medicine (의과대학) > Dept. of Neurosurgery (신경외과학교실) > 1. Journal Papers
1. College of Medicine (의과대학) > Dept. of Radiology (영상의학교실) > 1. Journal Papers

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