HMGB1 released from dead tumor cells after insufficient radiofrequency ablation promotes progression of HCC residual tumor via ERK1/2 pathway

Zhou, Yingshi; Zhang, Wenyue; Xu, Yanan; Zhang, Qi; Xiong, Shiyu; Tang, Haifeng; Luo, Bing Hao

doi:10.1080/02656736.2023.2174709

Cited by 7 publications

(9 citation statements)

References 44 publications

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“…Recently, extracellular HMGB1 was established to bind with RAGE, stimulate the development of drug resistance after chemotherapy and regulate autophagy and apoptosis in neighboring tumor cells [51,52]; the protein has also been proposed as a non-invasive marker for the detection of bladder carcinoma. Very recently HMGB1 released from dead tumor cells was proved to be a trigger of repopulation of the residual hepatocellular carcinoma cells after radiotherapy [53].…”

Section: Discussionmentioning

confidence: 99%

Autocrine regulation of tumor cell repopulation by Hsp70-HMGB1 alarmin complex

Sverchinsky,

Alhasan,

Mikeladze

et al. 2023

Preprint

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Background. Cancer recurrence is regulated by a variety of factors, among which is the material of dying tumor cells; it is suggested that remaining after anti-cancer therapy tumor cells receive a signal from proteins called damage-associated molecular patterns (DAMPs), one of which is heat shock protein 70 (Hsp70). Methods. Two models of tumor repopulation were employed, based on minimal population of cancer cells and application of conditioned medium (CM). To deplete the CMs of Hsp70 affinity chromatography on ATP-agarose and immunoprecipitation were used. Cell proliferation and the dynamics of cell growth were measured using MTT assay and xCELLigence technology; cell growth markers were estimated using qPCR and with the aid of ELISA for prostaglandin E detection. Immunoprecipitation followed by mass-spectrometry was employed to identify Hsp70-binding proteins and protein-protein interaction assays were developed to reveal the above protein complexes. Results. It was found that CM of dying tumor cells contains tumor regrowth-initiating factors and the removal of one of them, Hsp70, caused a reduction in the relapse-activating capacity. The pull out of Hsp70 alone using ATP-agarose had no effect on repopulation, while the immunodepletion of Hsp70 dramatically reduced its repopulation activity. Using proteomic and immunochemical approaches, we showed that Hsp70 in conditioned medium binds and binds another abundant alarmin, the High Mobility Group B1 (HMGB1) protein; the complex is formed in tumor cells treated with anti-cancer drugs, persists in the cytosol and is further released from dying tumor cells. Recurrence-activating power of Hsp70-HMGB1 complex was proved by the enhanced expression of proliferation markers, Ki67, Aurka and MCM-10 as well as by increase of prostaglandin E production and autophagy activation. Accordingly, dissociating the complex with Hsp70 chaperone inhibitors significantly inhibited the pro-growth effects of the above complex, in both in vitro and in vivo tumor relapse models. Conclusions. These data led us to suggest that the abundance of the Hsp70-HMGB1 complex in the extracellular matrix may serve as a novel marker of relapse state in cancer patients, while specific targeting of the complex may be promising in the treatment of cancers with a high risk of recurrence.

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Section: Discussionmentioning

confidence: 99%

Autocrine regulation of tumor cell repopulation by Hsp70-HMGB1 alarmin complex

Sverchinsky,

Alhasan,

Mikeladze

et al. 2023

Preprint

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“…However, when we added the complex to the depleted conditioned media, repopulation was restored. Several previous studies have been shown that exogenous HMGB1 promotes pro-survival autophagy and stimulates the tumor growth of gliomas [ 53 ] and esophageal squamous carcinoma [ 29 ], in addition to enhancing the chemoresistance of tumor cells in leukemic and bladder cancers [ 50 ]. Hence, we checked the expression of autophagy markers in A549 cells treated with either full Eto-CM or with Eto-CM depleted by specific anti-Hsp70 antibodies or with HMGB1-binding HBHP peptide.…”

Section: Discussionmentioning

confidence: 99%

“…All of these data convinced us that the Hsp70-HMGB1 complex can stimulate compensatory growth in tumor cell populations. It was previously reported that HMGB1 is able to promote tumor progression in prostate cancer [ 54 ] and pancreatic cancer [ 55 ] and enhance chemoresistance in acute leukemia [ 50 ] cells. Here we demonstrate that HMGB1 needs to be in complex with Hsp70 to perform the aforementioned pro-tumorigenic functions.…”

Section: Discussionmentioning

confidence: 99%

Autocrine regulation of tumor cell repopulation by Hsp70-HMGB1 alarmin complex

Sverchinsky,

Alhasan,

Mikeladze

et al. 2023

J Exp Clin Cancer Res

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Background Cancer recurrence is regulated by a variety of factors, among which is the material of dying tumor cells; it is suggested that remaining after anti-cancer therapy tumor cells receive a signal from proteins called damage-associated molecular patterns (DAMPs), one of which is heat shock protein 70 (Hsp70). Methods Two models of tumor repopulation were employed, based on minimal population of cancer cells and application of conditioned medium (CM). To deplete the CMs of Hsp70 affinity chromatography on ATP-agarose and immunoprecipitation were used. Cell proliferation and the dynamics of cell growth were measured using MTT assay and xCELLigence technology; cell growth markers were estimated using qPCR and with the aid of ELISA for prostaglandin E detection. Immunoprecipitation followed by mass-spectrometry was employed to identify Hsp70-binding proteins and protein-protein interaction assays were developed to reveal the above protein complexes. Results It was found that CM of dying tumor cells contains tumor regrowth-initiating factors and the removal of one of them, Hsp70, caused a reduction in the relapse-activating capacity. The pull out of Hsp70 alone using ATP-agarose had no effect on repopulation, while the immunodepletion of Hsp70 dramatically reduced its repopulation activity. Using proteomic and immunochemical approaches, we showed that Hsp70 in conditioned medium binds and binds another abundant alarmin, the High Mobility Group B1 (HMGB1) protein; the complex is formed in tumor cells treated with anti-cancer drugs, persists in the cytosol and is further released from dying tumor cells. Recurrence-activating power of Hsp70-HMGB1 complex was proved by the enhanced expression of proliferation markers, Ki67, Aurka and MCM-10 as well as by increase of prostaglandin E production and autophagy activation. Accordingly, dissociating the complex with Hsp70 chaperone inhibitors significantly inhibited the pro-growth effects of the above complex, in both in vitro and in vivo tumor relapse models. Conclusions These data led us to suggest that the abundance of the Hsp70-HMGB1 complex in the extracellular matrix may serve as a novel marker of relapse state in cancer patients, while specific targeting of the complex may be promising in the treatment of cancers with a high risk of recurrence.

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“…Traditional cancer treatment methods involve chemotherapy, surgery, and radiation therapy, which can somewhat alleviate the condition but often come with side effects. New noninvasive cancer treatment methods use specific physical and chemical means to target and destroy cancer or tumor cells without affecting other healthy cells, including immunotherapy, [108] gene therapy, [109] molecular targeted therapy, [110] hyperthermia, [111] radiofrequency ablation, [112] and others. Compared to traditional treatment methods such as chemotherapy, surgery, and radiation therapy, they are more effective with fewer side effects, can improve treatment efficiency, reduce side effectsHyperthermia has been a newly emerging method for treating of tumors and cancer in recent years, which has significant value in improving the treatment effect of traditional treatment methods.…”

Section: Photothermal Anti-tumor and Cancer Treatmentmentioning

confidence: 99%

Photothermal Conversion of Hydrogel‐Based Biomaterial

Wei

et al. 2023

The Chemical Record

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Traditional energy from fossil fuels like petroleum and coal is limited and contributes to global environmental pollution and climate change. Developing sustainable and eco‐friendly energy is crucial for addressing significant challenges such as climate change, energy dilemma and achieving the long‐term development of human society. Biomass hydrogels, which are easily synthesized and modified, have diverse sources and can be designed for different applications. They are being extensively researched for their applications in artificial intelligence, flexible sensing, biomedicine, and food packaging. The article summarizes recent advances in the preparation and applications of biomass‐based photothermal conversion hydrogels, discussing the light source, photothermal agents, matrix, and preparation methods in detail. It also explores the use of these hydrogels in seawater desalination, photothermal therapy, antibacterial agents, and light‐activated materials, offering new ideas for developing sustainable, efficient, and advanced photothermal conversion biomass hydrogel materials. The article concludes with suggestions for future research, highlighting the challenges and prospects in this field and paving the way for developing of long‐lasting, efficient energy materials.

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HMGB1 released from dead tumor cells after insufficient radiofrequency ablation promotes progression of HCC residual tumor via ERK1/2 pathway

Cited by 7 publications

References 44 publications

Autocrine regulation of tumor cell repopulation by Hsp70-HMGB1 alarmin complex

Autocrine regulation of tumor cell repopulation by Hsp70-HMGB1 alarmin complex

Autocrine regulation of tumor cell repopulation by Hsp70-HMGB1 alarmin complex

Photothermal Conversion of Hydrogel‐Based Biomaterial

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