Surface expression of a C-terminal α-helix region in heat shock protein 72 on murine LL/2 lung carcinoma can be recognized by innate immune sentinels

Tani, Fumito; Ohno, Minoru; Furukawa, Yoichi; Sakamoto, Masami; Masuda, Seiji; Kitabatake, Naofumi

doi:10.1016/j.molimm.2008.11.020

Cited by 5 publications

(5 citation statements)

References 58 publications

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“…In order to study the adaptive sEV-mediated communication under microenvironmental stress, we investigated cytostatic, heat and oxidative stress-induced alterations of the B16F1 mouse melanoma cell-derived sEVs. After verification the exosomal characteristics of our sEV isolates, we optimized the cytostatic and oxidative stress treatment conditions by proliferation assay and established the protocol for heat stress based on literature data 34 to expose the melanoma cells to sublethal stress conditions. Then, for the sEV production, we cultured the B16F1 cells under five different conditions in EV-depleted FBS-containing media; control cultures (Ctrl) received culture medium, cytostatic stressed cultures (Doxo) were treated with 0.6 µM doxorubicin, heat stressed cultures (Hs) were incubated at 42°C for 3 × 2 h, oxidative stressed cultures (Ag-TiO 2 ) were treated with 2.5 µg/ml light-induced Ag-TiO 2 , and as a control of the oxidative stress (Ag Ctrl), additional cultures were treated with illuminated media (Table 1).…”

Section: Resultsmentioning

confidence: 99%

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Small extracellular vesicles convey the stress-induced adaptive responses of melanoma cells

Harmati

Gyukity-Sebestyen

Dobra

et al. 2019

Sci Rep

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Exosomes are small extracellular vesicles (sEVs), playing a crucial role in the intercellular communication in physiological as well as pathological processes. Here, we aimed to study whether the melanoma-derived sEV-mediated communication could adapt to microenvironmental stresses. We compared B16F1 cell-derived sEVs released under normal and stress conditions, including cytostatic, heat and oxidative stress. The miRNome and proteome showed substantial differences across the sEV groups and bioinformatics analysis of the obtained data by the Ingenuity Pathway Analysis also revealed significant functional differences. The in silico predicted functional alterations of sEVs were validated by in vitro assays. For instance, melanoma-derived sEVs elicited by oxidative stress increased Ki-67 expression of mesenchymal stem cells (MSCs); cytostatic stress-resulted sEVs facilitated melanoma cell migration; all sEV groups supported microtissue generation of MSC-B16F1 co-cultures in a 3D tumour matrix model. Based on this study, we concluded that (i) molecular patterns of tumour-derived sEVs, dictated by the microenvironmental conditions, resulted in specific response patterns in the recipient cells; (ii) in silico analyses could be useful tools to predict different stress responses; (iii) alteration of the sEV-mediated communication of tumour cells might be a therapy-induced host response, with a potential influence on treatment efficacy.

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Section: Resultsmentioning

confidence: 99%

“…Parameters of the cytostatic and oxidative stresses were based on previous optimization by proliferation assay. Heat stress conditions were adapted from literature data 34 . In each group, 72 h supernatants of 6 parallel cell cultures were harvested, pooled and subjected to sEV isolation.…”

Section: Methodsmentioning

confidence: 99%

Small extracellular vesicles convey the stress-induced adaptive responses of melanoma cells

Harmati

Gyukity-Sebestyen

Dobra

et al. 2019

Sci Rep

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“…Given the role of some heat shock proteins, such as HSP70, in immunosurveillance [29–31], HSP inhibitors may abrogate the anti-cancer immune responses at the same time as eliminating cancer cells. Therefore, it will be important to establish the immunoregulatory role of HSPB1, if any, in further investigation of this protein.…”

Section: Discussionmentioning

confidence: 99%

“…HSP70 is perhaps the best studied in this regard, and HSP70 inhibitors have been shown to have anticancer effects [25–28]. However, the thermoregulatory role of HSP70 has the potential to be confused with its anti-immune activity [29–31]. Another heat shock protein, HSP27, is perhaps a better candidate.…”

Section: Introductionmentioning

confidence: 99%

HSPB1 deficiency sensitizes melanoma cells to hyperthermia induced cell death

et al. 2016

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Hyperthermia has shown clinical potency as a single agent or as adjuvant to other therapies in cancer treatment. However, thermotolerance induced by thermosensitive genes such as the heat shock proteins can limit the efficacy of hyperthermic treatment. In the present study, we identified HSPB1 (HSP27) is hyperthermically inducible or endogenously highly expressed in both murine and human melanoma cell lines. We used a siRNA strategy to reduce HSPB1 levels and showed increased intolerance to hyperthermia via reduced cell viability and/or proliferation of cells. In the investigation of underlying mechanisms, we found knock down of HSPB1 further increased the proportion of apoptotic cells in hyperthermic treated melanoma cells when compared with either single agent alone, and both agents leaded to cell cycle arrest at G0/G1 or G2/M phases. We concluded that hyperthermia combined with silencing of HSPB1 enhanced cell death and resulted in failure to thrive in melanoma cell lines, implying the potential clinical utility of hyperthermia in combination with HSPB1 inhibition in cancer treatment.

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“…Cells of the innate immune system: macrophages, dendritic cells and NK cells, are involved in the surveillance of functionally aberrant cells through the recognition of a specific C-terminal structure of Hsp72 a danger signal in living cells (Tani et al 2009). The expression of Hsp72 on the cell surface and release into the circulation might increase immune activity and subsequent cell damage in lung tissues following cigarette smoke exposure.…”

Section: Discussionmentioning

confidence: 99%

Effect of cigarette smoke and dexamethasone on Hsp72 system of alveolar epithelial cells

Gál

Aron

Szalay

et al. 2011

Cell Stress and Chaperones

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Smoking is the leading risk factor of chronic obstructive pulmonary disease (COPD) and lung cancer. Corticosteroids are abundantly used in these patients; however, the interaction of smoking and steroid treatment is not fully understood. Heat shock proteins (Hsps) play a central role in the maintenance of cell integrity, apoptosis and cellular steroid action. To better understand cigarette smoke-steroid interaction, we examined the effect of cigarette smoke extract (CSE) and/or dexamethasone (DEX) on changes of intracellular heat shock protein-72 (Hsp72) in lung cells. Alveolar epithelial cells (A549) were exposed to increasing doses (0; 0.1; 1; and 10 μM/μl) of DEX in the medium in the absence(C) and presence of CSE. Apoptosis, necrosis, Hsp72 messenger-ribonucleic acid (mRNA) and protein expression of cells were measured, and the role of Hsp72 on steroid effect examined. CSE reduced the number of viable cells by significantly increasing the number of apoptotic and necrotic cells. DEX dose-dependently decreased the ratio of apoptosis when CSE was administered, without change in necrosis. CSE - DEX co-treatment dose-dependently increased Hsp72 mRNA and protein expression, with the highest level measured in CSE + DEX (10) cells, while significantly lower levels were noted in all respective C groups. Pretreatment with Hsp72 silencing RNA confirmed that increased survival observed following DEX administration in CSE-treated cells was mainly mediated via the Hsp72 system. CSE significantly decreases cell survival by inducing apoptosis and necrosis. DEX significantly increases Hsp72 mRNA and protein expression only in the presence of CSE resulting in increased cellular protection and survival. DEX exerts its cell protective effects by decreasing apoptotic cell death via the Hsp72 system in CSE-treated alveolar epithelial cells.

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Surface expression of a C-terminal α-helix region in heat shock protein 72 on murine LL/2 lung carcinoma can be recognized by innate immune sentinels

Cited by 5 publications

References 58 publications

Small extracellular vesicles convey the stress-induced adaptive responses of melanoma cells

Small extracellular vesicles convey the stress-induced adaptive responses of melanoma cells

HSPB1 deficiency sensitizes melanoma cells to hyperthermia induced cell death

Effect of cigarette smoke and dexamethasone on Hsp72 system of alveolar epithelial cells

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