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Tumour‐associated macrophages as a novel target of VEGI‐251 in cancer therapy
- Source :
- Journal of Cellular and Molecular Medicine
- Publication Year :
- 2020
- Publisher :
- Wiley, 2020.
-
Abstract
- Tumour‐associated macrophages (TAMs), which possess M2‐like characters and are derived from immature monocytes in the circulatory system, represent a predominant population of inflammatory cells in solid tumours. TAM infiltration in tumour microenvironment can be used as an important prognostic marker in many cancer types and is a potential target for cancer prevention or treatment. VEGI‐251 not only is involved in the inhibition of tumour angiogenesis, but also participates in the regulation of host immunity. This work aimed to investigate the involvement of VEGI‐251 in the regulation of specific antitumour immunity. We found that recombinant human VEGI‐251(rhVEGI‐251) efficiently mediated the elimination of TAMs in tumour tissue in mice, and induced apoptosis of purified TAMs in vitro. During this process, caspase‐8 and caspase‐3 were activated, leading to PARP cleavage and apoptosis. Most importantly, we further elucidated the mechanism underlying VEGI‐251‐triggered TAM apoptosis, which suggests that ASK1, an intermediate component of the VEGI‐251, activates the JNK pathway via TRAF2 in a potentially DR3‐dependent manner in the process of TAM apoptosis. Collectively, our findings provide new insights into the basic mechanisms underlying the actions of VEGI‐251 that might lead to future development of antitumour therapeutic strategies using VEGI‐251 to target TAMs.
- Subjects :
- Models, Molecular
0301 basic medicine
TRAF2
Apoptosis
Immature Monocyte
law.invention
Mice
0302 clinical medicine
law
ASK1 signalling
Neoplasms
Tumor-Associated Macrophages
Tumor Microenvironment
ASK1
Molecular Targeted Therapy
skin and connective tissue diseases
education.field_of_study
VEGI 251
Recombinant Proteins
Caspases
030220 oncology & carcinogenesis
Recombinant DNA
Molecular Medicine
Original Article
Protein Binding
Signal Transduction
Tumor Necrosis Factor Ligand Superfamily Member 15
TAMs
Population
Antineoplastic Agents
Biology
Immunophenotyping
03 medical and health sciences
stomatognathic system
Cell Line, Tumor
Animals
Humans
education
Cell Proliferation
Cancer prevention
Endothelial Cells
Original Articles
Cell Biology
Xenograft Model Antitumor Assays
In vitro
Disease Models, Animal
030104 developmental biology
Cancer research
Carrier Proteins
Biomarkers
Subjects
Details
- ISSN :
- 15824934 and 15821838
- Volume :
- 24
- Database :
- OpenAIRE
- Journal :
- Journal of Cellular and Molecular Medicine
- Accession number :
- edsair.doi.dedup.....f53b953bbcc4beef98b2a54630ab3e31