HMGB1 Enhances Drug Resistance and Promotes <i>In Vivo</i> Tumor Growth of Lung Cancer Cells

Zhenghong,; ChenJia-Ning,; Yuxi,; Jiangping,; YuanLing,; ShenHong-Sheng,; ZhaoLi-Hong,; ChenPan-Feng,; YANGMin,

doi:10.1089/dna.2016.3360

Cited by 28 publications

(23 citation statements)

References 24 publications

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“…About 95% of EAC patients are prescribed cisplatin in the first-line setting ( 3 ). We discovered that seven proteomic expression trends associated with cisplatin resistance were seen to be either overexpressed or downregulated in the vast majority of EAC tumors analyzed in our study—HMGB1, IL-1RA, LGALS3BP, PRMT1, S100A8, SFN, and TXN ( 11 , 12 , 16 , 17 , 20 , 23 , 27 , 28 , 32 , 33 ). About 63% of EAC patients receive the chemotherapy drug 5-FU in the first-line setting ( 3 ).…”

Section: Resultsmentioning

confidence: 76%

“… The table includes the expression difference values between normal and tumor cells, the percentage of patients exhibiting these expression patterns, the descriptions of these markers involvement in other cancerous indications, potential drug types to target these markers, and reported associations to chemoresistance ( 12 , 15 , 16 , 21 , 25 – 27 , 32 , 34 ). 5-FU, fluorouracil; CRC, colorectal cancer; ESCC, esophageal squamous cell carcinoma; NSCLC, non-small cell lung carcinoma .…”

Section: Resultsmentioning

confidence: 99%

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Discovery of Novel and Clinically Relevant Markers in Formalin-Fixed Paraffin-Embedded Esophageal Cancer Specimen

et al. 2018

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Due to the ineffectiveness of chemoradiation and targeted therapy in esophageal anticancer care and the subsequent low survival rates, we constructed a high throughput method to discover and investigate new markers with prognostic, diagnostic, and therapeutic clinical utility. This was accomplished by developing a quick, inexpensive, and dependable platform to simultaneously quantify thousands of proteins which subsequently revealed novel markers involved in the pathogenesis of esophageal adenocarcinoma (EAC) via discovery mass spectrometry paired with conservative biostatistics. Our method uncovered a perfect storm of tumor suppressors being downregulated, proliferation markers ramped up, and chemoresistance markers overexpressed—many of which could serve as new therapy targets for EAC. The 12 markers discovered by this method are novel regarding their involvement in the pathogenesis of EAC. The molecular oncology arena now has a dozen new proteomic targets suitable for validation and elucidation of their clinical utility via gene knockdown in cellular and animal models. This new method can be replicated and applied to other cancers or disease states for research and development and discovery-based investigations. Our findings, which serve as a proof of concept, will hopefully motivate research groups to further expound on the molecular processes involved in the aggressiveness of EAC and other solid tumor diseases, ultimately leading to improved patient management strategies.

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Section: Resultsmentioning

confidence: 76%

Section: Resultsmentioning

confidence: 99%

Discovery of Novel and Clinically Relevant Markers in Formalin-Fixed Paraffin-Embedded Esophageal Cancer Specimen

et al. 2018

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“…Extracellular HMGB1 has a paracrine role, promoting the processing and presentation of tumor antigens by dendritic cells [28,29]. On the other hand, intracellular HMGB1 promotes growth, invasion and resistance of cancer cells to therapy, both in vitro and in vivo [30]. Assessing the TCGA database we found that high levels of HMGB1 are associated with poor prognosis in NSCLC, suggesting that the intracellular role is dominant (Additional file 4: Figure S4).…”

Section: Discussionmentioning

confidence: 94%

Damage-Associated Molecular Patterns (DAMPs) related to Immunogenic Cell Death are differentially triggered by clinically relevant chemotherapeutics in lung adenocarcinoma cells

Filippi-Chiela

Solari

Andrade

et al. 2019

Preprint

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Background Chemotherapeutics can stimulate immune antitumor response by inducing immunogenic cell death (ICD), which is characterized by the appearance of Damage-Associated Molecular Patterns (DAMPs) like the exposure of calreticulin (CRT) in cell surface, the release of ATP and the secretion of High Mobility Group Box 1 (HMGB1). Methods Here, our objective was to investigate levels of ICD-associated DAMPs induced by chemotherapeutics commonly used in the clinical practice of non-small cell lung cancer (NSCLC) and the prognosis values of these DAMPs.A549 human lung adenocarcinoma cells were treated with cisplatin, carboplatin, etoposide, paclitaxel and gemcitabine using clinically relevant conditions (doses, times and co-treatments). We assessed ICD-associated DAMPs, cell viability, apoptosis and autophagy in an integrated way. Results We found that cisplatin induced the highest levels of apoptosis, while carboplatin and etoposide were the less cytotoxic. Cisplatin also induced the highest levels of ICD-associated DAMPs, which was not incremented by co-treatments. Etoposide induced the lower levels of ICD and the highest levels of autophagy, suggesting that the cytoprotective role of autophagy is dominant in relation to its pro-ICD role. High levels of CRT were associated with better prognosis in TCGA databank. In an integrative analysis we found a strong negative correlation between cell number and ICD-associated DAMPs as well as between autophagy and ICD-associated DAMPs. We also purpose a mathematical integration of ICD-associated DAMPs in an index (InDAMPs) that may represent with greater biological relevance this process. Conclusions Cisplatin alone induced the highest levels of ICD-associated DAMPs, so that its combination with immunotherapies can be a promising therapeutic strategy in NSCLC.

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“…Extracellular HMGB1 has a paracrine role, promoting the processing and presentation of tumor antigens by dendritic cells [47,48]. On the other hand, intracellular HMGB1 promotes growth, invasion and resistance of cancer cells to therapy, both in vitro and in vivo [49]. Assessing the TCGA database we found that high levels of HMGB1 are associated with poor prognosis in NSCLC, suggesting that the intracellular role is dominant (Additional file 7: Fig.…”

Section: Discussionmentioning

confidence: 96%

Damage-associated molecular patterns (DAMPs) related to immunogenic cell death are differentially triggered by clinically relevant chemotherapeutics in lung adenocarcinoma cells

et al. 2020

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Background: Chemotherapeutics can stimulate immune antitumor response by inducing immunogenic cell death (ICD), which is activated by Damage-Associated Molecular Patterns (DAMPs) like the exposure of calreticulin (CRT) on the cell surface, the release of ATP and the secretion of High Mobility Group Box 1 (HMGB1). Methods: Here, we investigated the levels of ICD-associated DAMPs induced by chemotherapeutics commonly used in the clinical practice of non-small cell lung cancer (NSCLC) and the association of these DAMPs with apoptosis and autophagy. A549 human lung adenocarcinoma cells were treated with clinically relevant doses of cisplatin, carboplatin, etoposide, paclitaxel and gemcitabine. We assessed ICD-associated DAMPs, cell viability, apoptosis and autophagy in an integrated way. Results: Cisplatin and its combination with etoposide induced the highest levels of apoptosis, while etoposide was the less pro-apoptotic treatment. Cisplatin also induced the highest levels of ICD-associated DAMPs, which was not incremented by co-treatments. Etoposide induced the lower levels of ICD and the highest levels of autophagy, suggesting that the cytoprotective role of autophagy is dominant in relation to its pro-ICD role. High levels of CRT were associated with better prognosis in TCGA databank. In an integrative analysis we found a strong positive correlation between DAMPs and apoptosis, and a negative correlation between cell number and ICD-associated DAMPs as well as between autophagy and apoptosis markers. We also purpose a mathematical integration of ICDassociated DAMPs in an index (IndImunnog) that may represent with greater biological relevance this process. Cisplatin-treated cells showed the highest IndImmunog, while etoposide was the less immunogenic and the more pro-autophagic treatment.

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HMGB1 Enhances Drug Resistance and Promotes In Vivo Tumor Growth of Lung Cancer Cells

Cited by 28 publications

References 24 publications

Discovery of Novel and Clinically Relevant Markers in Formalin-Fixed Paraffin-Embedded Esophageal Cancer Specimen

Discovery of Novel and Clinically Relevant Markers in Formalin-Fixed Paraffin-Embedded Esophageal Cancer Specimen

Damage-Associated Molecular Patterns (DAMPs) related to Immunogenic Cell Death are differentially triggered by clinically relevant chemotherapeutics in lung adenocarcinoma cells

Damage-associated molecular patterns (DAMPs) related to immunogenic cell death are differentially triggered by clinically relevant chemotherapeutics in lung adenocarcinoma cells

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