Tumour hypoxia promotes melanoma growth and metastasis via High Mobility Group Box-1 and M2-like macrophages
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Tumour hypoxia promotes melanoma growth and metastasis via High Mobility Group Box-1 and M2-like macrophages. / Huber, Roman; Meier, Barbara; Otsuka, Atsushi; Fenini, Gabriele; Satoh, Takashi; Gehrke, Samuel; Widmer, Daniel; Levesque, Mitchell P; Mangana, Joanna; Kerl, Katrin; Gebhardt, Christoffer; Fujii, Hiroko; Nakashima, Chisa; Nonomura, Yumi; Kabashima, Kenji; Dummer, Reinhard; Contassot, Emmanuel; French, Lars E.
in: SCI REP-UK, Jahrgang 6, 18.07.2016, S. 29914.Publikationen: SCORING: Beitrag in Fachzeitschrift/Zeitung › SCORING: Zeitschriftenaufsatz › Forschung › Begutachtung
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TY - JOUR
T1 - Tumour hypoxia promotes melanoma growth and metastasis via High Mobility Group Box-1 and M2-like macrophages
AU - Huber, Roman
AU - Meier, Barbara
AU - Otsuka, Atsushi
AU - Fenini, Gabriele
AU - Satoh, Takashi
AU - Gehrke, Samuel
AU - Widmer, Daniel
AU - Levesque, Mitchell P
AU - Mangana, Joanna
AU - Kerl, Katrin
AU - Gebhardt, Christoffer
AU - Fujii, Hiroko
AU - Nakashima, Chisa
AU - Nonomura, Yumi
AU - Kabashima, Kenji
AU - Dummer, Reinhard
AU - Contassot, Emmanuel
AU - French, Lars E
PY - 2016/7/18
Y1 - 2016/7/18
N2 - Hypoxia is a hallmark of cancer that is strongly associated with invasion, metastasis, resistance to therapy and poor clinical outcome. Tumour hypoxia affects immune responses and promotes the accumulation of macrophages in the tumour microenvironment. However, the signals linking tumour hypoxia to tumour-associated macrophage recruitment and tumour promotion are incompletely understood. Here we show that the damage-associated molecular pattern High-Mobility Group Box 1 protein (HMGB1) is released by melanoma tumour cells as a consequence of hypoxia and promotes M2-like tumour-associated macrophage accumulation and an IL-10 rich milieu within the tumour. Furthermore, we demonstrate that HMGB1 drives IL-10 production in M2-like macrophages by selectively signalling through the Receptor for Advanced Glycation End products (RAGE). Finally, we show that HMGB1 has an important role in murine B16 melanoma growth and metastasis, whereas in humans its serum concentration is significantly increased in metastatic melanoma. Collectively, our findings identify a mechanism by which hypoxia affects tumour growth and metastasis in melanoma and depict HMGB1 as a potential therapeutic target.
AB - Hypoxia is a hallmark of cancer that is strongly associated with invasion, metastasis, resistance to therapy and poor clinical outcome. Tumour hypoxia affects immune responses and promotes the accumulation of macrophages in the tumour microenvironment. However, the signals linking tumour hypoxia to tumour-associated macrophage recruitment and tumour promotion are incompletely understood. Here we show that the damage-associated molecular pattern High-Mobility Group Box 1 protein (HMGB1) is released by melanoma tumour cells as a consequence of hypoxia and promotes M2-like tumour-associated macrophage accumulation and an IL-10 rich milieu within the tumour. Furthermore, we demonstrate that HMGB1 drives IL-10 production in M2-like macrophages by selectively signalling through the Receptor for Advanced Glycation End products (RAGE). Finally, we show that HMGB1 has an important role in murine B16 melanoma growth and metastasis, whereas in humans its serum concentration is significantly increased in metastatic melanoma. Collectively, our findings identify a mechanism by which hypoxia affects tumour growth and metastasis in melanoma and depict HMGB1 as a potential therapeutic target.
KW - Journal Article
U2 - 10.1038/srep29914
DO - 10.1038/srep29914
M3 - SCORING: Journal article
C2 - 27426915
VL - 6
SP - 29914
JO - SCI REP-UK
JF - SCI REP-UK
SN - 2045-2322
ER -