Angiogenesis in Uveal Melanoma

Jager, Martine J.

doi:10.1159/000095118

Cited by 7 publications

(7 citation statements)

References 16 publications

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“…Given that the choroid membrane is an intraocular blood vessel formed by endothelial cells (ECs) and that the “angiogenic switch” facilitates malignant transformation, serving as an important parameter in UM 26 , 27 , we then tested the role of nPD-L1 in tumor–ECs interactions during the tumorigenesis of UM (Fig. 2d ).…”

Section: Resultsmentioning

confidence: 99%

“…Extensive angiogenesis supports nutrient supplementation in malignancies and serves as a hallmark in cancers 39 , 40 . Since the uveal membrane is a vascular layer formed by ECs, crosstalk between ECs and tumors is essential for the oncogenesis of UM 26 , 41 . Higher vascular density in UM tumors was reported to be associated with greater aggressiveness and worse prognosis 42 , 43 .…”

Section: Discussionmentioning

confidence: 99%

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Nuclear PD-L1 promotes EGR1-mediated angiogenesis and accelerates tumorigenesis

Zhuang

et al. 2023

Cell Discov

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Targeting programmed cell death protein ligand 1 (PD-L1) remains one of the most essential immunotherapies in cancer1,2. PD-L1 has been detected in the nucleus in multiple malignancies, playing an oncogenic role independent of immune checkpoint regulation3–5. Howbeit, the regulatory function of nuclear PD-L1 (nPD-L1) remains to be fully understood. Here, we report that nPD-L1 is an endogenous accelerator for cancer angiogenesis. First, we found that an abundant proportion of PD-L1 was distributed within the nucleus of uveal melanoma samples, which is associated with an unfavorable outcome. Moreover, the capacity of promoting angiogenesis was largely attenuated in the nPD-L1-deficient cells both in vivo and in vitro. Mechanistically, nPD-L1 facilitates p-STAT3 binding to the promoter of early growth response-1 (EGR1), resulting in the activation of EGR1-mediated angiogenesis. Therapeutically, the inhibition of histone deacetylase 2 restores the normal acetylation level of PD-L1, blocking its nuclear translocation and thereby attenuating tumor angiogenesis. Conclusively, we reveal that nPD-L1 promotes angiogenesis in malignancies, and provide a novel anti-vascularization strategy through blocking aberrant PD-L1 nuclear translocation for tumor therapy.

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Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Nuclear PD-L1 promotes EGR1-mediated angiogenesis and accelerates tumorigenesis

Zhuang

et al. 2023

Cell Discov

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“…He proposed that ischaemia in the irradiated tissues could stimulate the secretion of proangiogenic factors. Recent studies have incriminated VEGF-A in this process and opened a new therapeutic window [5,6,7,10] . Our goal was either to stop the development of NVG or eliminate pain to avoid enucleation.…”

Section: Discussionmentioning

confidence: 99%

“…In recent years, Boyd et al [5] , Missotten et al [6] and Jager [7] have shown that vascular endothelial growth factor (VEGF) is involved in uveal melanomas, while Dunavoelgyi et al [8] and Vásquez et al [9] have demonstrated the efficacy of anti-VEGF in treating NVG. Thus, we have attempted to improve the control of NVG by performing intravitreal injections of ranibizumab.…”

Section: Introductionmentioning

confidence: 99%

Treatment of Neovascular Glaucoma after Proton Therapy for Uveal Melanomas with Ranibizumab Injection: Preliminary Results

et al. 2011

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A last-chance intravitreal injection of ranibizumab was administered alone or in combination with cryotherapy before enucleation for 14 melanomas with neovascular glaucoma (NVG) after proton therapy. These patients were uncontrolled despite medical treatment and experienced pain. All of our patients had a minimum of 4 months of follow-up (ranging from 4 to 22 months). In all of the cases, the neovessels disappeared, and the intra-ocular pressure was normal for 11 out of the 14 patients with or without antiglaucoma drops. No patient experienced pain after the first injection. Tumour regression increased in some patients. However, thus far, the number of cases has been too small to perform any statistical analyses. Although very promising, our results are only preliminary.

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“…Besides these, she introduced the use of oral valacyclovir for herpes keratitis, improved dry eye management with her step-wise approach, introduced ciclosporin for dry eye treatment in Leiden, introduced Moria trephine use for corneal transplantations, supervised the registry for corneal transplantation, developed the registry of uveal melanoma patients (for defining prognostication systems), developed a biobank for uveal melanoma, has been a part of The Cancer Genome Atlas, and was a part of the expert panel on Ocular Oncology AJCC Cancer Staging System 8 th Edition introduced in 2014 and contributed to the WHO 5 th edition “blue book” on ocular pathology. [ 6 7 8 ]…”

mentioning

confidence: 99%