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Inflammation Induce...
Inflammation Induced by MMP-9 Enhances Tumor Regression of Experimental Breast Cancer
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- Söderlund, Karin (author)
- Linköpings universitet,Onkologi,Hälsouniversitetet
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- Svensson, Susanne (author)
- Linköpings universitet,Onkologi,Hälsouniversitetet
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- Abrahamsson, Annelie (author)
- Linköpings universitet,Onkologi,Hälsouniversitetet
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- Bendrik, Christina (author)
- Linköpings universitet,Onkologi,Hälsouniversitetet
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- Robertson, Jennifer (author)
- McMaster University, Hamilton, Ontario, Canada
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- Gauldie, Jack (author)
- McMaster University, Hamilton, Ontario, Canada
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- Olsson, Anna-Karin (author)
- Uppsala universitet,Institutionen för medicinsk biokemi och mikrobiologi,Biochemistry and Molecular Cell Biology; Anna-Karin Olsson,Uppsala University, Sweden
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- Dabrosin, Charlotta (author)
- Östergötlands Läns Landsting,Linköpings universitet,Onkologi,Hälsouniversitetet,Onkologiska kliniken US
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(creator_code:org_t)
- 2013-04-15
- 2013
- English.
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In: Journal of Immunology. - : American Association of Immunologists. - 0022-1767 .- 1550-6606. ; 190:8, s. 4420-4430
- Related links:
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https://www.jimmunol...
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https://urn.kb.se/re...
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https://doi.org/10.4...
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https://urn.kb.se/re...
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Abstract
Subject headings
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- Matrix metalloproteinases (MMPs) have been suggested as therapeutic targets in cancer treatment, but broad-spectrum MMP inhibitors have failed in clinical trials. Recent data suggest that several MMPs including MMP-9 exert both pro-and antitumorigenic properties. This is also the case of the natural inhibitors of MMPs, tissue inhibitor of metalloproteinases (TIMPs). The inhibitor of MMP-9 is TIMP-1, and high levels of this enzyme have been associated with decreased survival in breast cancer. Inflammation is one hallmark of cancer progression, and MMPs/TIMPs may be involved in the local immune regulation. We investigated the role of MMP-9/TIMP-1 in regulating innate antitumor immunity in breast cancer. Breast cancers were established in nude mice and treated with intratumoral injections of adenoviruses carrying the human TIMP-1 or MMP-9 gene (AdMMP-9). In vivo microdialysis for sampling of cancer cell-derived (human) and stroma-derived (murine) proteins, immunostainings, as well as cell cultures were performed. We report a dose-dependent decrease of tumor growth and angiogenesis after AdMMP-9 treatment. In addition to increased generation of endostatin, AdMMP-9 promoted an antitumor immune response by inducing massive neutrophil infiltration. Neutrophil depletion prior to gene transfer abolished the therapeutic effects of AdMMP-9. Additionally, AdMMP-9 activated tumor-infiltrating macrophages into a tumor-inhibiting phenotype both in vivo and in vitro. AdMMP-9 also inhibited tumor growth in immune-competent mice bearing breast cancers. Adenoviruses carrying the human TIMP-1 gene had no effect on tumor growth or the immune response. Our novel data identify MMP-9 as a potent player in modulating the innate immune response into antitumor activities. The Journal of Immunology, 2013, 190: 4420-4430.
Keyword
- MEDICINE
- MEDICIN
Publication and Content Type
- ref (subject category)
- art (subject category)
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