Tumor-Promoting Activity and Proteomic Profiling of Cisplatin/Oxaliplatin-Derived DAMPs in Cholangiocarcinoma Cells

Damage-associated molecular patterns (DAMPs) are well recognized as the molecular signature of immunogenic cell death (ICD). The efficacy of drug-induced ICD function may be impacted by the precise ratio between immunostimulatory and immunoinhibitory DAMPs. Tumor-derived DAMPs can activate tumor-exp...

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Published inInternational journal of molecular sciences Vol. 23; no. 18; p. 10540
Main Authors Songjang, Worawat, Nensat, Chatchai, Nernpermpisooth, Nitirut, Seenak, Porrnthanate, Pankhong, Panyupa, Jumroon, Noppadon, Kumphune, Sarawut, Jiraviriyakul, Arunya
Format Journal Article
LanguageEnglish
Published Basel MDPI AG 11.09.2022
MDPI
Subjects
AKT protein
Apoptosis
Bioassays
Cancer therapies
Cell death
Cell growth
Chemotherapy
Cholangiocarcinoma
Cisplatin
Cytotoxicity
Damage patterns
DAMPs
Drugs
Heat shock proteins
HMGB1
HMGB1 protein
HSP
Immune system
Immunogenicity
Immunomodulation
Immunostimulation
Medical prognosis
Metastases
Oxaliplatin
Proteins
proteomic profiling
Proteomics
S100
Tumorigenesis
Tumors
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Summary:Damage-associated molecular patterns (DAMPs) are well recognized as the molecular signature of immunogenic cell death (ICD). The efficacy of drug-induced ICD function may be impacted by the precise ratio between immunostimulatory and immunoinhibitory DAMPs. Tumor-derived DAMPs can activate tumor-expressed TLRs for the promotion of tumor cell motility, invasion, metastatic spread and resistance to chemotherapeutic treatment. Herein, drug-induced DAMPs’ expression and their role in tumor progression are utilized as one crucial point of evaluation regarding chemotherapeutic treatment efficacy in our study. Cisplatin and oxaliplatin, the conventional anticancer chemotherapy drugs, are emphasized as a cause of well-known DAMPs’ release from cholangiocarcinoma (CCA) cells (e.g., HSP family, S100, CRT and HMGB1), whereby they trigger Akt, ERK and Cyclin-D1 to promote tumor activities. These findings strengthen the evidence that DAMPs are not only involved in immunomodulation but also in tumor promotion. Therefore, DAMP molecules should be considered as either targets of cancer treatment or biomarkers to evaluate treatment efficacy and tumor recurrence.
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ISSN:1422-0067
1661-6596
1422-0067
DOI:10.3390/ijms231810540