Effects of Adenosine on Lymphangiogenesis

Lenoir, Bénédicte; Wagner, Daniel R.; Blacher, Silvia; Sala-Newby, Graciela B.; Newby, Andrew C.; Noël, Agnès; Devaux, Yvan

doi:10.1371/journal.pone.0092715

Cited by 15 publications

(13 citation statements)

References 43 publications

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“…In this study, we provide conclusive evidence that signaling through the A2a adenosine receptor promotes lymphangiogenesis in response to inflammation and cancer, thereby favoring tumor cell metastasis to lymph nodes. Our findings support prior work from Lenoir et al, 43 which demonstrated pro-lymphangiogenenic properties of 2-chloro-adenosine in Matrigel plug assays.…”

Section: Discussionsupporting

confidence: 92%

Adenosine A2a receptor promotes lymphangiogenesis and lymph node metastasis

et al. 2019

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Section: Discussionsupporting

confidence: 92%

Adenosine A2a receptor promotes lymphangiogenesis and lymph node metastasis

et al. 2019

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“…Sponge assays were performed as previously described (45). In brief, gelfoam sponges (Pfizer, New York, NY, USA) fragments were soaked in conditioned medium.…”

Section: Sponge Assaysmentioning

confidence: 99%

Zonula occludens‐1/NF‐κB/CXCL8: a new regulatory axis for tumor angiogenesis

et al. 2017

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Zonula occludens-1 (ZO-1) is a submembrane scaffolding protein that may display proinvasive functions when it relocates from tight junctions into the cytonuclear compartment. This article examines the functional involvement of ZO-1 in CXCL8/IL-8 chemokine expression in lung and breast tumor cells. ZO-1 small interfering RNA and cDNA transfection experiments emphasized regulation of CXCL8/IL-8 expression a cytonuclear pool of ZO-1. Luciferase reporter assays highlighted a 173-bp region of promoter that responded to ZO-1. Moreover, by using mutated promoter constructs, we identified a NF-κB site as critical in this activation. Furthermore, NF-κB pathway signaling analysis revealed both IκBα and p65 phosphorylation in ZO-1-overexpressing cells, and subsequent p65 silencing validated its requirement for CXCL8/IL-8 induction. Investigation of the functional implication of this regulatory axis next showed the proangiogenic activity of ZO-1 in both o and angiogenesis assays. Finally, we found that non-small-cell lung carcinoma that presented a cytonuclear ZO-1 pattern was significantly more angiogenic that that without detectable cytonuclear ZO-1 expression. Taken together, our results demonstrate that ZO-1 regulates CXCL8/IL-8 expression the NF-κB signaling pathway and its p65 subunit, which subsequently modulates the transcription of IL-8. We also provide evidence of a newly identified regulatory pathway that could promote angiogenesis. Thus, our results support the concept that the ZO-1 shuttle from the cell junction to the cytonuclear compartment may affect both the intrinsic invasive properties of tumor cells and the establishment of the protumoral microenvironment.-Lesage, J., Suarez-Carmona, M., Neyrinck-Leglantier, D., Grelet, S., Blacher, S., Hunziker, W., Birembaut, P., Noël, A., Nawrocki-Raby, B., Gilles, C., Polette, M. Zonula occludens-1/NF-κB/CXCL8: a new regulatory axis for tumor angiogenesis.

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“…ADO is an immunosuppressive metabolite produced at high levels within the TME and contributes, through different mechanisms, to the progression of the tumor itself [ 43 , 44 ]. The effects of a wide range of ADO concentrations (from 10 nM to 100 µM) on U343MG proliferation and viability were evaluated after 24 or 48 h of cell treatment.…”

Section: Resultsmentioning

confidence: 99%

High Adenosine Extracellular Levels Induce Glioblastoma Aggressive Traits Modulating the Mesenchymal Stromal Cell Secretome

Pietrobono

Giacomelli

Marchetti

et al. 2020

IJMS

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Glioblastoma is an aggressive, fast-growing brain tumor influenced by the composition of the tumor microenvironment (TME) in which mesenchymal stromal cell (MSCs) play a pivotal role. Adenosine (ADO), a purinergic signal molecule, can reach up to high micromolar concentrations in TME. The activity of specific adenosine receptor subtypes on glioma cells has been widely explored, as have the effects of MSCs on tumor progression. However, the effects of high levels of ADO on glioma aggressive traits are still unclear as is its role in cancer cells-MSC cross-talk. Herein, we first studied the role of extracellular Adenosine (ADO) on isolated human U343MG cells as a glioblastoma cellular model, finding that at high concentrations it was able to prompt the gene expression of Snail and ZEB1, which regulate the epithelial–mesenchymal transition (EMT) process, even if a complete transition was not reached. These effects were mediated by the induction of ERK1/2 phosphorylation. Additionally, ADO affected isolated bone marrow derived MSCs (BM-MSCs) by modifying the pattern of secreted inflammatory cytokines. Then, the conditioned medium (CM) of BM-MSCs stimulated with ADO and a co-culture system were used to investigate the role of extracellular ADO in GBM–MSC cross-talk. The CM promoted the increase of glioma motility and induced a partial phenotypic change of glioblastoma cells. These effects were maintained when U343MG cells and BM-MSCs were co-cultured. In conclusion, ADO may affect glioma biology directly and through the modulation of the paracrine factors released by MSCs overall promoting a more aggressive phenotype. These results point out the importance to deeply investigate the role of extracellular soluble factors in the glioma cross-talk with other cell types of the TME to better understand its pathological mechanisms.

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Effects of Adenosine on Lymphangiogenesis

Cited by 15 publications

References 43 publications

Adenosine A2a receptor promotes lymphangiogenesis and lymph node metastasis

Adenosine A2a receptor promotes lymphangiogenesis and lymph node metastasis

Zonula occludens‐1/NF‐κB/CXCL8: a new regulatory axis for tumor angiogenesis

High Adenosine Extracellular Levels Induce Glioblastoma Aggressive Traits Modulating the Mesenchymal Stromal Cell Secretome

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