The antitumoral effects of chemerin are independent from leukocyte recruitment and mediated by inhibition of neoangiogenesis

Dubois-Vedrenne, Ingrid; Delbany, Diana D.A.D. Al; Henau, Olivier De; Robert, Virginie; Vernimmen, Maxime; Langa, Francina; Lefort, Anne; Libert, Frédérick; Wittamer, Valérie; Parmentier, Marc

doi:10.18632/oncotarget.28056

Cited by 9 publications

(14 citation statements)

References 60 publications

(96 reference statements)

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“…In our hands, chemerin had no effects on neovessel sprouting in the aorta ring assay, nor on migration or proliferation of HUVECs in culture. It should be noted however that we reported recently a strong inhibitory effect of chemerin on the extent of the capillary network formed by HUVECs in the bead sprouting assay [21].…”

Section: Discussionmentioning

confidence: 60%

“…We used B16-F0 melanoma and Lewis lung carcinoma (LLC), two models reported to progress in an angiogenesis-dependent manner [38,39]. As reported previously [21], grafting B16-F0 or LLC cells in K5-Chem mice resulted in smaller tumors than in control mice (Fig. 8a-c).…”

Section: Chemerin Destabilizes Blood Vessels In Tumor Modelsmentioning

confidence: 70%

“…Chemerin was also described to display anti-tumoral properties in a number of cancer models, as well as protumoral effects in some others [54]. In previous studies, we described the anti-tumoral properties of chemerin in several models of cancer [19,21]. These effects were attributed to an inhibition of tumoral neoangiogenesis, leading to hypoxia and necrosis.…”

Section: Discussionmentioning

confidence: 91%

“…Chemerin was shown to display anti-tumoral properties in several mouse models [18,20]. In a recent study, we reported that these properties could be attributed to an inhibitory effect on the vascularization of tumors, resulting in necrotic cell death [21]. We investigated further whether this anti-angiogenic effect in a tumoral context could be mediated by a destabilization of neovessels.…”

Section: Chemerin Destabilizes Blood Vessels In Tumor Modelsmentioning

confidence: 95%

“…We and others have identified chemerin as an anti-tumoral factor in different mouse models [18][19][20]. We recently proposed that, in mouse cancer graft models, the anti-tumoral activity of chemerin does not involve the recruitment of leukocyte populations but is mediated by the inhibition of the vascularization of the tumors, an effect mediated through CMKLR1 [21].…”

Section: Introductionmentioning

confidence: 99%

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Chemerin regulates normal angiogenesis and hypoxia-driven neovascularization

et al. 2021

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Chemerin is a multifunctional protein initially characterized in our laboratory as a chemoattractant factor for leukocyte populations. Its main functional receptor is CMKLR1. We identified previously chemerin as an anti-tumoral factor inhibiting the vascularization of tumor grafts. We show here that overexpression of bioactive chemerin in mice results in a reduction of the density of the retinal vascular network during its development and in adults. Chemerin did not affect vascular sprouting during the post-natal development of the network, but rather promoted endothelial cell apoptosis and vessel pruning. This phenotype was reversed to normal in CMKLR1-deficient mice, demonstrating the role of this receptor. Chemerin inhibited also neoangiogenesis in a model of pathological proliferative retinopathy, and in response to hind-limb ischemia. Mechanistically, PTEN and FOXO1 antagonists could almost completely restore the density of the retinal vasculature, suggesting the involvement of the PI3-kinase/AKT pathway in the chemerin-induced vessel regression process.

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Section: Discussionmentioning

confidence: 60%

Section: Chemerin Destabilizes Blood Vessels In Tumor Modelsmentioning

confidence: 70%

Section: Discussionmentioning

confidence: 91%

Section: Chemerin Destabilizes Blood Vessels In Tumor Modelsmentioning

confidence: 95%

Section: Introductionmentioning

confidence: 99%

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Chemerin regulates normal angiogenesis and hypoxia-driven neovascularization

et al. 2021

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Chemerin enhances mesenchymal features of glioblastoma by establishing autocrine and paracrine networks in a CMKLR1-dependent manner

Shen

Liu

et al. 2022

Oncogene

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Glioblastoma multiforme (GBM) with mesenchymal features exhibits enhanced chemotherapeutic resistance and results in reduced overall survival. Recent studies have suggested that there is a positive correlation between the GBM mesenchymal status and immune cell infiltration. However, the mechanisms by which GBM acquires its mesenchymal features in a tumor immune microenvironment-dependent manner remains unknown. Here, we uncovered a chemerin-mediated autocrine and paracrine network by which the mesenchymal phenotype of GBM cells is strengthened. We identified chemerin as a prognostic secretory protein mediating the mesenchymal phenotype-promoting network between tumor-associated macrophages (TAMs) and tumor cells in GBM. Mechanistically, chemerin promoted the mesenchymal features of GBM by suppressing the ubiquitin-proteasomal degradation of CMKLR1, a chemerin receptor predominantly expressed on TAMs and partially expressed on GBM cells, thereby enhancing NF-κB pathway activation. Moreover, chemerin was found to be involved in the recruitment of TAMs in the GBM tumor microenvironment. We revealed that chemerin also enhances the mesenchymal phenotype-promoting ability of TAMs and promotes their M2 polarization via a CMKLR1/NF-κB axis, which further exacerbates the mesenchymal features of GBM. Blocking the chemerin/CMKLR1 axis with 2-(α-naphthoyl) ethyltrimethylammonium iodide disrupted the mesenchymal network and suppressed tumor growth in GBM. These results suggest the therapeutic potential of targeting the chemerin/CMKLR1 axis to block the mesenchymal network in GBM.

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Chemerin in immunity

Laffranchi,

Schioppa,

Sozio

et al. 2024

Journal of Leukocyte Biology

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Chemerin is a distant member of the cystatin protein family, initially discovered as a chemotactic factor and subsequently also reported to act as adipokine and angiogenetic factor. The biological activity of chemerin is regulated at different levels, such as gene expression, protein processing, and interaction with both signaling and nonsignaling receptors. Chemerin is mostly produced by stromal cells, such as adipocytes, fibroblasts, and epithelial and endothelial cells, and circulates in almost all human tissues as a zymogen that needs to be proteolytically activated to exert its biological functions. At the receptor level, chemerin binds a G protein-coupled 7-transmembrane domain receptor Chemerin1 (also named ChemR23 and CMKLR1), mostly expressed by innate immune cells, such as macrophages, dendritic cells, and natural killer cells, and by border cells. In addition, chemerin may bind GPR1, a weak signaling receptor, and CCRL2, a nonsignaling receptor expressed by barrier cells, such as endothelial and epithelial cells, able to regulate leukocytes’ migration by multiple mechanisms. The aim of this review is to summarize the contribution of chemerin in the regulation of immune responses.

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The antitumoral effects of chemerin are independent from leukocyte recruitment and mediated by inhibition of neoangiogenesis

Cited by 9 publications

References 60 publications

Chemerin regulates normal angiogenesis and hypoxia-driven neovascularization

Chemerin regulates normal angiogenesis and hypoxia-driven neovascularization

Chemerin enhances mesenchymal features of glioblastoma by establishing autocrine and paracrine networks in a CMKLR1-dependent manner

Chemerin in immunity

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