Knockout of HIF-1α in tumor-associated macrophages enhances M2 polarization and attenuates their pro-angiogenic responses

• Verfasst von: Werno, Christian [VerfasserIn]
• Verfasst von: Menrad, Heidi [VerfasserIn]
• Verfasst von: Weigert, Andreas [VerfasserIn]
• Verfasst von: Dehne, Nathalie [VerfasserIn]
• Verfasst von: Goerdt, Sergij [VerfasserIn]
• Verfasst von: Schledzewski, Kai [VerfasserIn]
• Verfasst von: Kzhyshkowska, Julia [VerfasserIn]
• Verfasst von: Brüne, Bernhard [VerfasserIn]
• Titel: Knockout of HIF-1α in tumor-associated macrophages enhances M2 polarization and attenuates their pro-angiogenic responses
• Verf.angabe: Christian Werno, Heidi Menrad, Andreas Weigert, Nathalie Dehne, Sergij Goerdt, Kai Schledzewski, Julia Kzhyshkowska and Bernhard Brüne
• E-Jahr: 2010
• Jahr: [October 2010]
• Umfang: 10 S.
• Illustrationen: Illustrationen
• Fussnoten: Published: 28 April 2010 ; Gesehen am 29.11.2023
• Titel Quelle: Enthalten in: Carcinogenesis
• Ort Quelle: Oxford : Oxford Univ. Press, 1980
• Jahr Quelle: 2010
• Band/Heft Quelle: 31(2010), 10 vom: Okt., Seite 1863-1872
• ISSN Quelle: 1460-2180
• DOI: doi:10.1093/carcin/bgq088
• Datenträger: Online-Ressource
• Sprache: eng
• K10plus-PPN: 187158115X

Abstract

Tumor-associated macrophages (TAMs) constitute major infiltrates of solid tumors and express a marker profile that characterizes alternatively activated macrophages (MФs). TAMs accumulate in hypoxic tumor regions, express high amounts of hypoxia-inducible factor-1 (HIF-1) and contribute to tumor angiogenesis and invasiveness. However, the precise role of HIF-1 on MФ infiltration and phenotype alterations remains poorly defined. Therefore, we cocultured wild type (wt) versus HIF-1α −/− MФs with tumor spheroids. Both, wt and HIF-1α −/− MФs, infiltrated hypoxic regions of tumor spheroids at equal rates and got alternatively activated. Interestingly, significantly higher amounts of HIF-1α −/− MФs expressed the TAM markers CD206 and stabilin-1 compared with wt phagocytes. Stimulation of infiltrated TAMs with lipopolysaccharide (LPS)/interferon-γ revealed a reduced expression of the pro-inflammatory markers interleukin (IL)-6, tumor necrosis factor-α and inducible nitric oxide synthase in HIF-1α −/− MФs. Furthermore, HIF-1α −/− MФs were less cytotoxic toward tumor cells. Although infiltration of MФs increased the invasive potential of tumor spheroids independently of HIF-1, the ability to stimulate differentiation of stem cells toward CD31-positive cells was triggered by wt but not by HIF-1α −/− MФs. Our data suggest that HIF-1α-deficient MФs develop a more prominent TAM marker profile accompanied by reduced cytotoxicity, whereas HIF-1 seems indispensable for the angiogenesis-promoting properties of TAMs.