Regulation of VEGF-A in Uveal Melanoma

Filali, Mariam el; Missotten, Guy S.; Maat, Willem; Ly, Long V.; Luyten, Gregorius P M; Velden, Pieter A. van der; Jager, Martine J.

doi:10.1167/iovs.09-4739

Cited by 64 publications

(59 citation statements)

References 35 publications

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“…Jager's group measured serum VEGF levels in normal subjects and compared these levels to the level in UM patients immediately before the primary treatment. 12 They found levels lower than reported here (167 and 183 pg/ml, respectively). Similar to our findings, they have reported a very large range of VEGF between the tested subjects without any statistical difference between the two groups.…”

Section: Discussioncontrasting

confidence: 60%

VEGF as a Biomarker for Metastatic Uveal Melanoma in Humans

Barak

Pe’er

Kalickman

et al. 2011

Current Eye Research

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Serum VEGF increased significantly after metastases developed. However, the wide inter-patient variance precludes the use of any cut-off level to determine the metastatic status of an individual patient based on a single VEGF serum level. An increase in VEGF on serial measurements may indicate the development of metastases. Further investigation is warranted to assess VEGF's value as a predictive marker for metastatic disease.

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Section: Discussioncontrasting

confidence: 60%

VEGF as a Biomarker for Metastatic Uveal Melanoma in Humans

Barak

Pe’er

Kalickman

et al. 2011

Current Eye Research

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“…47 Exposing uveal melanoma cells in vitro to a hypoxic environment induced increased vascular endothelial growth factor production. 48 There is no doubt that hypoxia has an important role in cancer; however, whether such hypoxia induces macrophage migration and differentiation in uveal melanoma is still not known.…”

Section: Impact Of Oxygen Availabilitymentioning

confidence: 99%

Inflammation in uveal melanoma

Bronkhorst

Jager

2012

Eye

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Leukocytic infiltration is a common feature of human cancers, including those that develop in immunoprivileged sites, such as the eye. The infiltration of myeloid and T cells into tumours is part of the host response against cancer. In uveal melanoma, high densities of immune cells seem to be involved in tumour progression, as they are associated with the loss of one chromosome 3. The nature of this tumour microenvironment might offer therapeutic opportunities.

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“…Of the two pathways the first appeared to be the most important in the progression of uveal melanomas as, in the present analysis, the pVEGFR2/KDR expression was associated with prognosis. In this context, an increased VEGF and mRNA expression has been documented in uveal melanomas, compared to normal ocular tissues in previous studies [28,29], and VEGF levels were significantly higher in patients with metastatic disease [21]. Increased serum VEGF levels have been also considered as a marker of metastatic uveal melanoma [30].…”

Section: Discussionmentioning

confidence: 87%

“…[20]. el Filali et al, on the other hand, were able to confirm the hypoxic induction of HIF1a and that of VEGF in uveal melanoma cell lines which, however, were not linked to enhanced proliferation [21]. In a series of cutaneous malignant melanomas high HIF1a expression was noted in 87% of tumors, but overexpression was not linked with other prognostic variables or the overall disease specific survival [22].…”

Section: Discussionmentioning

confidence: 97%

Phosphorylated pVEGFR2/KDR receptor expression in uveal melanomas: relation with HIF2α and survival

Giatromanolaki

Sivridis

Bechrakis

et al. 2011

Clin Exp Metastasis

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Hypoxia and its down-stream activated pathways are commonly involved in tumor progression. Genes involved in angiogenesis and glycolysis, i.e. vascular endothelial growth factor (VEGF) and lactase dehydrogenase A (LDHA), respectively, are transcriptionally controlled by the hypoxia inducible factors 1α and 2α (HIF1α and HIF2α). A series of 60 uveal melanomas were immunohistochemically assessed for the expression of VEGF and the phosphorylated/activated form of VEGF receptor 2 (pVEGFR2/KDR), after binding to VEGF. The expression of HIF1α, HIF2α and LDH5 was also investigated. Uveal melanomas overexpressing HIF2α (but not that of HIF1α) were significantly associated with high VEGF (P = 0.005), pVEGFR2/KDR (P < 0.0001) and LDH5 (P ≤ 0.0001). High LDH5 was linked with tumor necrosis (P = 0.01) and increased tumor size (P = 0.03). High VEGF was linked with phosphorylated pVEGFR2/KDR receptors. In univariate analysis high pVEGFR2/KDR receptor expression was significantly related with poor prognosis (P = 0.02). It is concluded that HIF2α plays an important role in the progression of uveal melanomas possibly by promoting the autocrine loop VEGF-pVEGFR2/KDR, and by enhancing the expression of LDHA gene, conferring thus a growth advantage. As pVEGFR2/KDR expression was significantly related with poor prognosis, inhibitors of this receptor may improve the clinical outcome of patients with pVEGFR2/KDR overexpressing uveal melanomas.

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Regulation of VEGF-A in Uveal Melanoma

Abstract: VEGF-A expression by UM cells is mainly controlled by hypoxia and involves the HIF-1alpha pathway, thus indicating an important role for the tumor cell environment. Metastases led to increased serum VEGF-A levels, indicating that VEGF-A may be involved in the growth of metastases.

Cited by 64 publications

References 35 publications

VEGF as a Biomarker for Metastatic Uveal Melanoma in Humans

VEGF as a Biomarker for Metastatic Uveal Melanoma in Humans

Inflammation in uveal melanoma

Phosphorylated pVEGFR2/KDR receptor expression in uveal melanomas: relation with HIF2α and survival

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