Different measures of HMGB1 location in cancer immunology

Gorgulho, Carolina Mendonça; Murthy, Pranav; Liotta, Lance; Espina, Virginia; Lotze, Michael T.

doi:10.1016/bs.mie.2019.10.011

Cited by 11 publications

(2 citation statements)

References 103 publications

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“…High mobility group box 1 (Hmgb1) is one of the DAMPs, which are released from necrotic cells and induce Tnfsf11 expression in osteoblast lineage cells by promoting the production of proinflammatory cytokines, including tumor necrosis factor α (TNF-α), interleukin (IL)-6, and IL-1, in macrophages, dendritic cells, monocytes, and neutrophils [23]. Hmgb1 is normally localized in the nucleus and translocated to the cytosol with many types of cellular stress [24]. Thus, we examined the localization of Hmgb1 protein using femoral sections.…”

Section: Plos Geneticsmentioning

confidence: 99%

Runx2 is essential for the transdifferentiation of chondrocytes into osteoblasts

et al. 2020

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Chondrocytes proliferate and mature into hypertrophic chondrocytes. Vascular invasion into the cartilage occurs in the terminal hypertrophic chondrocyte layer, and terminal hypertrophic chondrocytes die by apoptosis or transdifferentiate into osteoblasts. Runx2 is essential for osteoblast differentiation and chondrocyte maturation. Runx2-deficient mice are composed of cartilaginous skeletons and lack the vascular invasion into the cartilage. However, the requirement of Runx2 in the vascular invasion into the cartilage, mechanism of chondrocyte transdifferentiation to osteoblasts, and its significance in bone development remain to be elucidated. To investigate these points, we generated Runx2fl/flCre mice, in which Runx2 was deleted in hypertrophic chondrocytes using Col10a1 Cre. Vascular invasion into the cartilage was similarly observed in Runx2fl/fl and Runx2fl/flCre mice. Vegfa expression was reduced in the terminal hypertrophic chondrocytes in Runx2fl/flCre mice, but Vegfa was strongly expressed in osteoblasts in the bone collar, suggesting that Vegfa expression in bone collar osteoblasts is sufficient for vascular invasion into the cartilage. The apoptosis of terminal hypertrophic chondrocytes was increased and their transdifferentiation was interrupted in Runx2fl/flCre mice, leading to lack of primary spongiosa and osteoblasts in the region at E16.5. The osteoblasts appeared in this region at E17.5 in the absence of transdifferentiation, and the number of osteoblasts and the formation of primary spongiosa, but not secondary spongiosa, reached to levels similar those in Runx2fl/fl mice at birth. The bone structure and volume and all bone histomophometric parameters were similar between Runx2fl/fl and Runx2fl/flCre mice after 6 weeks of age. These findings indicate that Runx2 expression in terminal hypertrophic chondrocytes is not required for vascular invasion into the cartilage, but is for their survival and transdifferentiation into osteoblasts, and that the transdifferentiation is necessary for trabecular bone formation in embryonic and neonatal stages, but not for acquiring normal bone structure and volume in young and adult mice.

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Section: Plos Geneticsmentioning

confidence: 99%

Runx2 is essential for the transdifferentiation of chondrocytes into osteoblasts

et al. 2020

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“…In the cytoplasm, HMGB1 induces autophagy by binding to Beclin-1 and regulates mitochondrial quality (5). In the extracellular matrix, HMGB1 functions as a damage-associated molecule that participates in multiple cellular activities, including cell-cell interactions, pro-inflammatory cytokine production, cell proliferation, differentiation, invasion and autophagy (4,6). The dysregulation of HMGB1 has been shown to be associated with a number of diseases, particularly cancer.…”

Section: Introductionmentioning

confidence: 99%

Starvation insult induces the translocation of high mobility group box 1 to cytosolic compartments in glioma

Cui,

Yao,

Jia

2023

Oncol Rep

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High mobility group box 1 (HMGB1) is a highly conserved and ubiquitous nuclear protein in eukaryotic cells. In response to stress, it transfers from the nucleus to the cytoplasm and finally, to the extracellular matrix, participating in inflammation and carcinogenesis. Increased HMGB1 protein levels are frequently associated with the reduced survival of patients with glioma. HMGB1 plays contextual roles depending on its subcellular localization. However, the mechanisms underlying its subcellular localization and secretion remain unclear. In the present study, the subcellular localization and secretion of HMGB1 in starved glioma cells were investigated using immunofluorescence microscopy, enzyme-linked immunosorbent assay, subcellular fractionation, western blotting and immunoelectron microscopy. The results demonstrated that starvation induced HMGB1 translocation from the nucleus to the cytoplasm and finally, to the extracellular milieu in glioma cells. HMGB1 was localized in the mitochondria, endoplasmic reticulum (ER), peroxisomes, autophagosomes, lysosomes, endosomes and the cytoskeleton. Immunoelectron microscopy confirmed that HMGB1 was present within or around cytosolic compartments. Subcellular fractionation further demonstrated that HMGB1 transferred to membrane-bound compartments. In addition, HMGB1 was localized to specific contact areas between the ER and mitochondria, known as mitochondria-associated membranes. On the whole, the results of the present study suggest that starvation induces HMGB1 secretion, which can be inhibited through the suppression of autophagy. Starvation insult induces HMGB1 translocation to the cytosolic compartments of glioma cells, and autophagy may be involved in the extracellular secretion of HMGB1 in starved glioma cells.

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Elevated expression of HMGB1 is prognostic of poor survival in patients with relapsed/refractory T/NK-CL

Wang

Jie

et al. 2021

Ann Hematol

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Different measures of HMGB1 location in cancer immunology

Cited by 11 publications

References 103 publications

Runx2 is essential for the transdifferentiation of chondrocytes into osteoblasts

Runx2 is essential for the transdifferentiation of chondrocytes into osteoblasts

Starvation insult induces the translocation of high mobility group box 1 to cytosolic compartments in glioma

Elevated expression of HMGB1 is prognostic of poor survival in patients with relapsed/refractory T/NK-CL

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