Elevated circulating Hsp70 levels are correlative for malignancies in different mammalian species

Salvermoser, Lukas; Flisikowski, Krzysztof; Dressel, Susann; Nytko, Katarzyna J.; Bley, Carla Rohrer; Schnieke, Angelika; Samt, Ann-Kathrin; Thölke, Dennis; Lennartz, Philipp; Schwab, Melissa; Wang, Fei; Dezfouli, Ali Bashiri; Multhoff, Gabriele

doi:10.1007/s12192-022-01311-y

Cited by 3 publications

(2 citation statements)

References 79 publications

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“…This reflects that most Hsp70 in the circulation is of liposomal origin. Recent study shows similar results in healthy dogs and cats 26,35 as determined with the compHsp70 ELISA which is based on the same Hsp70 antibodies and reagents like the exoHsp70 ELISA. These findings are in line with data reported in the current study regarding tumour‐bearing animals.…”

Section: Discussionsupporting

confidence: 57%

Extracellular heat shock protein 70 levels in tumour‐bearing dogs and cats treated with radiation therapy and hyperthermia

Nytko,

Weyland,

Dressel‐Böhm

et al. 2023

Vet Comparative Oncology

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Hyperthermia is a form of a cancer treatment which is frequently applied in combination with radiotherapy (RT) to improve therapy responses and radiosensitivity. The mode of action of hyperthermia is multifactorial; the one hand by altering the amount of the blood circulation in the treated tissue, on the other hand by modulating molecular pathways involved in cell survival processes and immunogenic interactions. One of the most dominant proteins induced by hyperthermia is the major stress‐inducible heat shock protein 70 (Hsp70). Hsp70 can be found in the blood either as a free‐protein (free HSP70) derived from necrotic cells, or lipid‐bound (liposomal Hsp70) when it is actively released in extracellular vesicles (EVs) by living cells. The aim of the study was to evaluate the levels of free and liposomal Hsp70 before and after treatment with RT alone or hyperthermia combined with radiotherapy (HTRT) in dogs and cats to evaluate therapy responses. Peripheral blood was collected from feline and canine patients before and at 2, 4, 6 and 24 h after treatment with RT or HTRT. Hsp70 enzyme‐linked immunosorbent assays (ELISAs) were performed to determine the free and liposomal Hsp70 concentrations in the serum. The levels were analysed after the first fraction of radiation to study immediate effects and after all applied fractions to study cumulative effects. The levels of free and liposomal Hsp70 levels in the circulation were not affected by the first singular treatment and cumulative effects of RT in cats however, after finalizing all treatment cycles with HTRT free and liposomal Hsp70 levels significantly increased. In dogs, HTRT, but not treatment with RT alone, significantly affected liposomal Hsp70 levels during the first fraction. Free Hsp70 levels were significantly increased after RT, but not HTRT, during the first fraction in dogs. In dogs, on the other hand, RT alone resulted in a significant increase in liposomal Hsp70, but HTRT did not significantly affect the liposomal Hsp70 when cumulative effects were analysed. Free Hsp70 was significantly induced in dogs after both, RT and HTRT when cumulative effects were analysed. RT and HTRT treatments differentially affect the levels of free and liposomal Hsp70 in dogs and cats. Both forms of Hsp70 could potentially be further investigated as potential liquid biopsy markers to study responses to RT and HTRT treatment in companion animals.

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Section: Discussionsupporting

confidence: 57%

Extracellular heat shock protein 70 levels in tumour‐bearing dogs and cats treated with radiation therapy and hyperthermia

Nytko,

Weyland,

Dressel‐Böhm

et al. 2023

Vet Comparative Oncology

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“…Conserved proteins are similar proteins that appear in each exosome and include cluster of differentiation (CD) 36, CD81, CD9, CD82 ( 29 , 30 ). Heat shock protein (Hsp) 500, Hsp70, Hsp90, ALIX, and tumor susceptibility gene 101 (TSG101) ( 31 – 33 ),which serve as pan-markers for the common detection of exosomes ( 34 ). The composition of exosome-specific proteins depends on the cellular origin of the exosome and may change depending on the physiological changes and stimuli acting on the cell; for example, exosomes derived from mesenchymal stem cells or stromal cells (MSC) are endowed with immunosuppressive and tumor-homing capabilities ( 18 ).…”

Section: Exosome-derived Mirnasmentioning

confidence: 99%

Exosome-derived microRNAs: emerging players in vitiligo

li,

Pang,

et al. 2024

Front. Immunol.

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Exosome-derived microRNAs (miRNAs) are biomacromolecules and nanoscale extracellular vesicles originating from intracellular compartments that are secreted by most cells into the extracellular space. This review examines the formation and function of exosomal miRNAs in biological information transfer, explores the pathogenesis of vitiligo, and highlights the relationship between exosomal miRNAs and vitiligo. The aim is to deepen the understanding of how exosomal miRNAs influence immune imbalance, oxidative stress damage, melanocyte-keratinocyte interactions, and melanogenesis disorders in the development of vitiligo. This enhanced understanding may contribute to the development of potential diagnostic and therapeutic options for vitiligo.

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Extracellular Hsp70 and Circulating Endometriotic Cells as Novel Biomarkers for Endometriosis

Guder,

Heinrich,

Seifert-Klauss

et al. 2024

IJMS

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Stress-inducible heat shock protein 70 (Hsp70), which functions as a molecular chaperone and is frequently overexpressed in different cancer cell types, is present on the cell surface of tumor cells and is actively released into the circulation in free and extracellular lipid vesicle-associated forms. Since the exact pathomechanism of endometriosis has not yet been elucidated (although it has been associated with the development of endometrial and ovarian cancer), we asked whether extracellular Hsp70 and circulating endometriotic cells (CECs) reflect the presence and development of endometriosis. Therefore, circulating levels of free and lipid microvesicle-associated Hsp70 were measured using the Hsp70-exo ELISA, and the presence of circulating CECs in the peripheral blood of patients with endometriosis was determined using membrane Hsp70 (mHsp70) and EpCAM monoclonal antibody (mAb)-based bead isolation approaches. Isolated CECs were further characterized by immunofluorescence using reagents directed against cytokeratin (epithelial marker), CD45 (leukocyte marker), CD105/CD44 (mesenchymal stemness markers) and by comparative RNA analysis. Similar to the situation in patients with cancer, the levels of circulating Hsp70 were elevated in the blood of patients with histologically proven endometriosis compared to a healthy control cohort, with significantly elevated Hsp70 levels in endometriosis patients with lesions outside the uterine cavity. Moreover, CECs could be isolated using the cmHsp70.1 mAb-based, and to a lesser extent EpCAM mAb-based, bead approach in all patients with endometriosis, with the highest counts obtained using the mHsp70-targeting procedure in patients with extra-uterine involvement. The longevity in cell culture and the expression of the cytokeratins CD105 and CD44, together with differentially expressed genes related to epithelial-to-mesenchymal transition (EMT), revealed similarities between mHsp70-expressing CECs and circulating tumor cells (CTCs) and suggest a mesenchymal stem cell origin. These findings support the involvement of mHsp70-positive stem cell-like cells in the development of endometriotic lesions. In summary, elevated levels of Hsp70 and CECs in the circulation could serve as liquid biopsy markers for endometriosis with extra-uterine involvement and help to elucidate the underlying pathomechanism of the disease.

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Elevated circulating Hsp70 levels are correlative for malignancies in different mammalian species

Cited by 3 publications

References 79 publications

Extracellular heat shock protein 70 levels in tumour‐bearing dogs and cats treated with radiation therapy and hyperthermia

Extracellular heat shock protein 70 levels in tumour‐bearing dogs and cats treated with radiation therapy and hyperthermia

Exosome-derived microRNAs: emerging players in vitiligo

Extracellular Hsp70 and Circulating Endometriotic Cells as Novel Biomarkers for Endometriosis

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