ArticlePLoS computational biology2015
Angiogenic activity of breast cancer patients' monocytes reverted by combined use of systems modeling and experimental approaches.
Article in PLoS computational biology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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Who cites it
14 citing papers in PubMed, 23 citations in OpenAlex.
- Trial
- Tumor-associated macrophages in anti-PD-1/PD-L1 immunotherapy for hepatocellular carcinoma: recent research progress.Frontiers in pharmacology · 2024Review
- Understanding the role of endothelial cells in brain tumor formation and metastasis: a proposition to be explored for better therapy.Journal of the National Cancer Center · 2023Review
- Reprogramming tumor-associated macrophages as a unique approach to target tumor immunotherapy.Frontiers in immunology · 2023Review
- Tumor-Associated Macrophages: Reasons to Be Cheerful, Reasons to Be Fearful.Experientia supplementum (2012) · 2022Article
- Macrophage Polarization States in the Tumor Microenvironment.International journal of molecular sciences · 2021Review
- Consensus guidelines for the use and interpretation of angiogenesis assays.Angiogenesis · 2018Review
- Drug Resistance Mechanisms in Colorectal Cancer Dissected with Cell Type-Specific Dynamic Logic Models.Cancer research · 2017Article
- Looking beyond the cancer cell for effective drug combinations.Genome medicine · 2016Article
- Social networks help to infer causality in the tumor microenvironment.BMC research notes · 2016Article
- Bevacizumab specifically decreases elevated levels of circulating KIT+CD11b+ cells and IL-10 in metastatic breast cancer patients.Oncotarget · 2016Article
- TIE-2-expressing monocytes are lymphangiogenic and associate specifically with lymphatics of human breast cancer.Oncoimmunology · 2016Article
- Toward a rational design of combination therapy in cancer.Oncoimmunology · 2015Article
- TIE-2 expressing monocytes in human cancers.OncoimmunologyArticle
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Authors and funding
21 authors at 8 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Angiogenesis plays a key role in tumor growth and cancer progression. TIE-2-expressing monocytes (TEM) have been reported to critically account for tumor vascularization and growth in mouse tumor experimental models, but the molecular basis of their pro-angiogenic activity are largely unknown. Moreover, differences in the pro-angiogenic activity between blood circulating and tumor infiltrated TEM in human patients has not been established to date, hindering the identification of specific targets for therapeutic intervention. In this work, we investigated these differences and the phenotypic reversal of breast tumor pro-angiogenic TEM to a weak pro-angiogenic phenotype by combining Boolean modelling and experimental approaches. Firstly, we show that in breast cancer patients the pro-angiogenic activity of TEM increased drastically from blood to tumor, suggesting that the tumor microenvironment shapes the highly pro-angiogenic phenotype of TEM. Secondly, we predicted in silico all minimal perturbations transitioning the highly pro-angiogenic phenotype of tumor TEM to the weak pro-angiogenic phenotype of blood TEM and vice versa. In silico predicted perturbations were validated experimentally using patient TEM. In addition, gene expression profiling of TEM transitioned to a weak pro-angiogenic phenotype confirmed that TEM are plastic cells and can be reverted to immunological potent monocytes. Finally, the relapse-free survival analysis showed a statistically significant difference between patients with tumors with high and low expression values for genes encoding transitioning proteins detected in silico and validated on patient TEM. In conclusion, the inferred TEM regulatory network accurately captured experimental TEM behavior and highlighted crosstalk between specific angiogenic and inflammatory signaling pathways of outstanding importance to control their pro-angiogenic activity. Results showed the successful in vitro reversion of such an activity by perturbation of in silico predicted target genes in tumor derived TEM, and indicated that targeting tumor TEM plasticity may constitute a novel valid therapeutic strategy in breast cancer.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.