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Epithelial HMGB1 delays skin wound healing and drives tumor initiation by priming neutrophils for NET formation

Esther Hoste (UGent) , Christian Maueröder (UGent) , Lisette Van Hove (UGent) , Leen Catrysse (UGent) , Hanna-Kaisa Vikkula (UGent) , Mozes Sze (UGent) , Bastiaan Maes (UGent) , Dyah Karjosukarso, Liesbet Martens (UGent) , Amanda Gonçalves (UGent) , et al.
(2019) CELL REPORTS. 29(9). p.2689-2701
Author
Organization
Abstract
Regenerative responses predispose tissues to tumor formation by largely unknown mechanisms. High-mobility group box 1 (HMGB1) is a danger-associated molecular pattern contributing to inflammatory pathologies. We show that HMGB1 derived from keratinocytes, but not myeloid cells, delays cutaneous wound healing and drives tumor formation. In wounds of mice lacking HMGB1 selectively in keratinocytes, a marked reduction in neutrophil extracellular trap (NET) formation is observed. Pharmacological targeting of HMGB1 or NETs prevents skin tumorigenesis and accelerates wound regeneration. HMGB1-dependent NET formation and skin tumorigenesis is orchestrated by tumor necrosis factor (TNF) and requires RIPK1 kinase activity. NETs are present in the microenvironment of keratinocyte-derived tumors in mice and lesional and tumor skin of patients suffering from recessive dystrophic epidermolysis bullosa, a disease in which skin blistering predisposes to tumorigenesis. We conclude that tumorigenicity of the wound microenvironment depends on epithelial-derived HMGB1 regulating NET formation, thereby establishing a mechanism linking reparative inflammation to tumor initiation.
Keywords
GROUP BOX 1, EXTRACELLULAR TRAP FORMATION, EPIDERMAL-CELLS, NECROSIS-FACTOR, STEM-CELLS, MICE, EXPRESSION, RECEPTOR, RELEASE, NETOSIS

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MLA
Hoste, Esther, et al. “Epithelial HMGB1 Delays Skin Wound Healing and Drives Tumor Initiation by Priming Neutrophils for NET Formation.” CELL REPORTS, vol. 29, no. 9, 2019, pp. 2689–701.
APA
Hoste, E., Maueröder, C., Van Hove, L., Catrysse, L., Vikkula, H.-K., Sze, M., … van Loo, G. (2019). Epithelial HMGB1 delays skin wound healing and drives tumor initiation by priming neutrophils for NET formation. CELL REPORTS, 29(9), 2689–2701.
Chicago author-date
Hoste, Esther, Christian Maueröder, Lisette Van Hove, Leen Catrysse, Hanna-Kaisa Vikkula, Mozes Sze, Bastiaan Maes, et al. 2019. “Epithelial HMGB1 Delays Skin Wound Healing and Drives Tumor Initiation by Priming Neutrophils for NET Formation.” CELL REPORTS 29 (9): 2689–2701.
Chicago author-date (all authors)
Hoste, Esther, Christian Maueröder, Lisette Van Hove, Leen Catrysse, Hanna-Kaisa Vikkula, Mozes Sze, Bastiaan Maes, Dyah Karjosukarso, Liesbet Martens, Amanda Gonçalves, Eef Parthoens, Ria Roelandt, Wim Declercq, Ignacia Fuentes, Francis Palisson, Sergio Gonzalez, Julio C Salas-Alanis, Louis Boon, Peter Huebener, Klaas Willem Mulder, Kodi Ravichandran, Yvan Saeys, Robert Felix Schwabe, and Geert van Loo. 2019. “Epithelial HMGB1 Delays Skin Wound Healing and Drives Tumor Initiation by Priming Neutrophils for NET Formation.” CELL REPORTS 29 (9): 2689–2701.
Vancouver
1.
Hoste E, Maueröder C, Van Hove L, Catrysse L, Vikkula H-K, Sze M, et al. Epithelial HMGB1 delays skin wound healing and drives tumor initiation by priming neutrophils for NET formation. CELL REPORTS. 2019;29(9):2689–701.
IEEE
[1]
E. Hoste et al., “Epithelial HMGB1 delays skin wound healing and drives tumor initiation by priming neutrophils for NET formation,” CELL REPORTS, vol. 29, no. 9, pp. 2689–2701, 2019.
@article{8639600,
  abstract     = {Regenerative responses predispose tissues to tumor formation by largely unknown mechanisms. High-mobility group box 1 (HMGB1) is a danger-associated molecular pattern contributing to inflammatory pathologies. We show that HMGB1 derived from keratinocytes, but not myeloid cells, delays cutaneous wound healing and drives tumor formation. In wounds of mice lacking HMGB1 selectively in keratinocytes, a marked reduction in neutrophil extracellular trap (NET) formation is observed. Pharmacological targeting of HMGB1 or NETs prevents skin tumorigenesis and accelerates wound regeneration. HMGB1-dependent NET formation and skin tumorigenesis is orchestrated by tumor necrosis factor (TNF) and requires RIPK1 kinase activity. NETs are present in the microenvironment of keratinocyte-derived tumors in mice and lesional and tumor skin of patients suffering from recessive dystrophic epidermolysis bullosa, a disease in which skin blistering predisposes to tumorigenesis. We conclude that tumorigenicity of the wound microenvironment depends on epithelial-derived HMGB1 regulating NET formation, thereby establishing a mechanism linking reparative inflammation to tumor initiation.},
  author       = {Hoste, Esther and Maueröder, Christian and Van Hove, Lisette and Catrysse, Leen and Vikkula, Hanna-Kaisa and Sze, Mozes and Maes, Bastiaan and Karjosukarso, Dyah and Martens, Liesbet and Gonçalves, Amanda and Parthoens, Eef and Roelandt, Ria and Declercq, Wim and Fuentes, Ignacia and Palisson, Francis and Gonzalez, Sergio and Salas-Alanis, Julio C and Boon, Louis and Huebener, Peter and Mulder, Klaas Willem and Ravichandran, Kodi and Saeys, Yvan and Schwabe, Robert Felix and van Loo, Geert},
  issn         = {2211-1247},
  journal      = {CELL REPORTS},
  keywords     = {GROUP BOX 1,EXTRACELLULAR TRAP FORMATION,EPIDERMAL-CELLS,NECROSIS-FACTOR,STEM-CELLS,MICE,EXPRESSION,RECEPTOR,RELEASE,NETOSIS},
  language     = {eng},
  number       = {9},
  pages        = {2689--2701},
  title        = {Epithelial HMGB1 delays skin wound healing and drives tumor initiation by priming neutrophils for NET formation},
  url          = {http://dx.doi.org/10.1016/j.celrep.2019.10.104},
  volume       = {29},
  year         = {2019},
}

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