The DOI matches its Crossref record; 10 of the 10 references it cites were found in a registry or an index.
Knockout of HIF-1 in tumor-associated macrophages enhances M2 polarization and attenuates their pro-angiogenic responses
Open accessAbstract
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.
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Cites
Targeting HIF-1 for cancer therapy
Semenza, G. L. (2003) · Nature Reviews Cancer · doi:10.1038/nrc1187 · Cited by 6,717
MANTOVANI, A., SOZZANI, S., LOCATI, M., ALLAVENA, P., & SICA, A. (2002) · Trends in Immunology · doi:10.1016/s1471-4906(02)02302-5 · Cited by 5,528
Tumorigenesis and the angiogenic switch
Bergers, G., & Benjamin, L. E. (2003) · Nature reviews. Cancer · doi:10.1038/nrc1093 · Cited by 3,559
Regulation of angiogenesis by hypoxia: role of the HIF system
Pugh, C. W., & Ratcliffe, P. J. (2003) · Nature Medicine · doi:10.1038/nm0603-677 · Cited by 2,520
Bingle, L., Brown, N. J., & Lewis, C. E. (2002) · The Journal of Pathology · doi:10.1002/path.1027 · Cited by 2,022
Colony-Stimulating Factor 1 Promotes Progression of Mammary Tumors to Malignancy
Lin, E. Y., Nguyen, A. V., Russell, R. G., & Pollard, J. W. (2001) · The Journal of Experimental Medicine · doi:10.1084/jem.193.6.727 · Cited by 1,594
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Macrophages Regulate the Angiogenic Switch in a Mouse Model of Breast Cancer
Lin, E. Y., Li, J.-F., Gnatovskiy, L., Deng, Y., Zhu, L., Grzesik, D. A., Qian, H., Xue, X.-N., & Pollard, J. W. (2006) · Cancer Research · doi:10.1158/0008-5472.can-06-1278 · Cited by 1,074
“Re-educating” tumor-associated macrophages by targeting NF-κB
Hagemann, T., Lawrence, T., McNeish, I., Charles, K. A., Kulbe, H., Thompson, R. G., Robinson, S. C., & Balkwill, F. R. (2008) · The Journal of Experimental Medicine · doi:10.1084/jem.20080108 · Cited by 792
Bacterial lipopolysaccharide induces HIF-1 activation in human monocytes via p44/42 MAPK and NF-κB
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Cited by
Hypoxia-inducible factors and the response to hypoxic stress
Majmundar, A. J., Wong, W. J., & Simon, M. C. (2010) · Molecular Cell · doi:10.1016/j.molcel.2010.09.022 · Cited by 2,380
HIF‐1 at the crossroads of hypoxia, inflammation, and cancer
Balamurugan, K. (2016) · International Journal of Cancer · doi:10.1002/ijc.29519 · Cited by 572
Capece, D., Fischietti, M., Verzella, D., Gaggiano, A., Cicciarelli, G., Tessitore, A., Zazzeroni, F., & Alesse, E. (2013) · BioMed Research International · doi:10.1155/2013/187204 · Cited by 408
Redox control of inflammation in macrophages
Brüne, B., Dehne, N., Grossmann, N., Jung, M., Namgaladze, D., Schmid, T., von Knethen, A., & Weigert, A. (2013) · Antioxidants & Redox Signaling · doi:10.1089/ars.2012.4785 · Cited by 377
Self-citationHypoxia‐inducible factors in regulation of immune responses in tumour microenvironment
Kumar, V., & Gabrilovich, D. I. (2014) · Immunology · doi:10.1111/imm.12380 · Cited by 329
Metadata
- Authors
- Werno, C., Menrad, H., Weigert, A., Dehne, N., Goerdt, S., Schledzewski, K., Kzhyshkowska, J., & Brune, B.
- Venue
- Carcinogenesis
- Publisher
- Oxford University Press (OUP)
- Published
- 2010-04-28
- Volume
- 31
- Issue
- 10
- Pages
- 1863-1872
- ISSN
- 0143-3334 (ISSN-L)
- 1460-2180
- OpenAlex
- W2138272556
- Cited by
- 167
- References
- 10
- FWCI
- 4.33
- Type
- journal article
- Language
- en
- Open access
- bronze
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- Werno, C., Menrad, H., Weigert, A., Dehne, N., Goerdt, S., Schledzewski, K., Kzhyshkowska, J., & Brune, B. (2010). Knockout of HIF-1 in tumor-associated macrophages enhances M2 polarization and attenuates their pro-angiogenic responses. Carcinogenesis. https://doi.org/10.1093/carcin/bgq088
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