Interleukin‐34 promotes tumor progression and metastatic process in osteosarcoma through induction of angiogenesis and macrophage recruitment
Open accessAbstract
Interleukin‐34 (IL‐34) was recently characterized as the M‐CSF “twin” cytokine, regulating the proliferation/differentiation/survival of myeloid cells. The implication of M‐CSF in oncology was initially suspected by the reduced metastatic dissemination in knock‐out mice, due to angiogenesis impairment. Based on this observation, our work studied the involvement of IL‐34 in the pathogenesis of osteosarcoma. The in vivo effects of IL‐34 were assessed on tissue vasculature and macrophage infiltration in a murine preclinical model based on a paratibial inoculation of human osteosarcoma cells overexpressing or not IL‐34 or M‐CSF.In vitro investigations using endothelial cell precursors and mature HUVEC cells were performed to analyse the involvement of IL‐34 in angiogenesis and myeloid cell adhesion. The data revealed that IL‐34 overexpression was associated with the progression of osteosarcoma (tumor growth, lung metastases) and an increase of neo‐angiogenesis.In vitro analyses demonstrated that IL‐34 stimulated endothelial cell proliferation and vascular cord formation. Pre‐treatment of endothelial cells by chondroitinases/heparinases reduced the formation of vascular tubes and abolished the associated cell signalling. In addition, IL‐34 increased the in vivo recruitment of M2 tumor‐associated macrophages into the tumor tissue. IL‐34 increased in vitro monocyte/CD34+cell adhesion to activated HUVEC monolayers under physiological shear stress conditions. This work also demonstrates that IL‐34 is expressed by osteosarcoma cells, is regulated by TNF‐α, IL‐1β, and contributes to osteosarcoma growth by increasing the neo‐angiogenesis and the recruitment of M2 macrophages. By promoting new vessel formation and extravasation of immune cells, IL‐34 may play a key role in tumor development and inflammatory diseases.
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Well-established cell lines have facilitated investigation into mechanisms of malignancy and high-throughput screens to identify osteosarcoma vulnerabilities.
“Well-established cell lines, such as SaOS, MG63, KHOS, MNNG-HOS, U2OS and OS-17, have facilitated investigation into mechanisms of malignancy 206,207 and high-throughput screens to identify osteosarcoma vulnerabilities 92,208 .”
From Osteosarcoma (2022) · cites this paper as [206]
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- Authors
- Ségaliny, A. I., Mohamadi, A., Dizier, B., Lokajczyk, A., Brion, R., Lanel, R., Amiaud, J., Charrier, C., Boisson‐Vidal, C., & Heymann, D.
- Affiliations
- Inserm (FR)
- Corresponding author
- Boisson‐Vidal, Catherine
- Heymann, Dominique
- ORCID
- Venue
- International Journal of Cancer
- Publisher
- Wiley
- Published
- 2014-12-13
- Volume
- 137
- Issue
- 1
- Pages
- 73-85
- ISSN
- 0020-7136 (ISSN-L)
- 1097-0215
- OpenAlex
- W1915719235
- Cited by
- 199
- References
- 57
- Citations by year
- 2026: 7 · 2025: 14 · 2024: 14 · 2023: 23 · 2022: 17 · 2021: 21 · 2020: 27 · 2019: 17 · 2018: 25 · 2017: 12 · 2016: 16 · 2015: 6
- FWCI
- 4.64
- Type
- journal article
- Language
- en
- Open access
- green
- inserm.hal.science
- Licence
- Locations
- International Journal of Cancer (publishedVersion)
- PubMed (publishedVersion)
- White Rose Research Online (University of Leeds, The University of Sheffield, University of York) (acceptedVersion)
- HAL (submittedVersion, other-oa)
- Funders
- Ligue Nationale contre le Cancer (Equipe Ligue 2012)
- Region des Pays de la Loire (CIMATH II)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Angiogenesis and VEGF in Cancer
- Life Sciences › Immunology and Microbiology › Immunology › Immune cells in cancer
- Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Sarcoma Diagnosis and Treatment
- Keywords
- IL-34, osteosarcoma, tumor angiogenesis, metastasis, M2 tumor-associated macrophages, macrophage recruitment, macrophage colony-stimulating factor, endothelial cell proliferation, TNF-α, IL-1β, tumor growth, lung metastasis
- MeSH terms
- Animals, Bone Neoplasms, Cells, Cultured, Humans, Interleukins, Lung Neoplasms, Macrophages, Neoplasm Transplantation, Neovascularization, Pathologic, Osteosarcoma, Tumor Necrosis Factor-alpha, Gene Expression Regulation, Neoplastic, Cell Proliferation, Mice, Interleukin-1beta, Human Umbilical Vein Endothelial Cells, In Vitro Techniques
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