Serum vascular endothelial growth factor (VEGF) levels correlate with number and location of micrometastases in a murine model of uveal melanoma

Crosby, Meredith E.; Yang, Hua; Gao, Weiqing; Zhang, Lane; Grossniklaus, Hans E.

doi:10.1136/bjo.2010.182402

Cited by 24 publications

(20 citation statements)

References 18 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…El-Shabrawi et al have shown that MMP-9 is predominantly expressed in highly aggressive uveal melanoma cells (32). A recent report showed that high level of VEGFA was correlated with the number and location of micrometastases in a murine model of uveal melanoma (33). In this study, we observed that MMP-2, MMP-9, and VEGFA altered in the same pattern as NF-κB1.…”

Section: Discussionsupporting

confidence: 66%

MicroRNA-9 suppresses uveal melanoma cell migration and invasion through the NF-κB1 pathway

et al. 2012

View full text Add to dashboard Cite

Abstract. The aggressive course of uveal melanoma is believed to reflect its unusually invasive and metastatic nature, which is associated with the nuclear factor kappaB (NF-κB) pathway. MicroRNAs (miRNAs) have been implicated in the regulation of various biological and pathological processes in cancer, however, the special role of miR-9 in uveal melanoma metastasis is largely unknown. In the present study, we showed that miR-9 is significantly reduced in highly invasive uveal melanoma cell lines, and suppressed migration and invasion of highly invasive cells. Furthermore, miR-9 negatively modulated NF-κB1 expression by direct targeting at its 3'-UTRs. Additionally, downstream targets of NF-κB1, such as MMP-2, MMP-9 and VEGFA, were regulated by miR-9 in the same pattern as NF-κB1. Therefore, miR-9 suppresses uveal melanoma cell migration and invasion partly through downregulation of the NF-κB1 signaling pathway.

show abstract

Section: Discussionsupporting

confidence: 66%

MicroRNA-9 suppresses uveal melanoma cell migration and invasion through the NF-κB1 pathway

et al. 2012

View full text Add to dashboard Cite

show abstract

“…The need for blood biomarkers for uveal melanoma has become more—and not less—urgent in the era of the molecular prognostication. The work reported by Crosby et al 3 provides support to those involved in this important effort.…”

mentioning

confidence: 66%

“…VEGF production by tumours and cells in the tumour environment is a critical step in the formation and progression of metastasis 3. Foremost is that the serum VEGF levels are measurable when liver metastases are microscopic, suggesting that testing may have the requisite sensitivity.…”

mentioning

confidence: 99%

Blood biomarkers of uveal melanoma metastasis

Triozzi

Singh

2010

British Journal of Ophthalmology

View full text Add to dashboard Cite

“…Currently, there are limited studies in the literature investigating VEGF-A expression in UM, and fewer assessing the inhibition of this cytokine in animal models, thus comprehensive studies regarding VEGF-A in multiple UM cell lines are needed [25, 26, 29, 40]. In the present study, we determined that three UM cell lines produced copious amounts of VEGF-A (between 4600 and 12,000 pg/μL).…”

Section: Discussionmentioning

confidence: 78%

“…In vitro studies have also revealed that UM cell lines produce VEGF-A in normal culture and production increases under hypoxic conditions [23, 24]. Furthermore, in an animal model of UM, increased VEGF-A levels were detectable in serum, and these escalations correlate with increased metastasis [25]. Reports vary with regard to VEGF-A positivity in primary UM tumours, ranging from 22% to 84%, and there are conflicting reports regarding correlations between expression levels and tumour size, vascularisation, or metastasis [26, 27].…”

Section: Introductionmentioning

confidence: 99%

ecancermedicalscience

Logan

Burnier²,

Burnier³

View full text Add to dashboard Cite

Background:Uveal melanoma (UM) is a disease that affects approximately five people per million in the United States. This disease metastasises predominantly to the liver, and treatment options following the clinical detection of these sequelae are limited. Vascular endothelial growth factor-A (VEGF-A) is the primary activator of tumour angiogenesis and functions by binding to VEGF-Receptor 2 (VEGF-R2) and is often required for tumour growth beyond 2–3 mm. The purpose of this study was to investigate the expression of VEGF-A and the primary VEGF-R2 in three UM cell lines. Furthermore, we investigated the effects of VEGF-A inhibition on receptor activation and production of other cytokines. Finally, the effects of VEGF-A inhibition on the proliferation, migration, and invasion in the cell lines were ascertained.Materials:Three UM cell lines (92.1, OCM-1, and UW-1) were incubated with and without the addition of 100 μg/mL of bevacizumab. VEGF-A expression under both conditions was determined by sandwich enzyme-linked immunosorbent assay (ELISA), and phosphorylated VEGF-R2 expression was determined using western blot. The effects of VEGF-A inhibition on 20 cytokines (IL-1a, IL-2, IL-5, IL-8, IL-12p70, GM-CSF, IFNy, CCL3, MMP-9, TNF-a, IL-1b, IL-4, IL-6, IL-10, IL-13, GRO, MCP-1, MIP-1b, and RANTES) were determined using a multiplex sandwich ELISA. Proliferation rates before and after treatment were evaluated via sulforhodamine B assay, and migration and invasion assays implementing the Boyden chamber technique, the latter with artificial extracellular matrix, were used to assess their respective abilities. The Student’s t-test was used to compare changes in cytokine expression following VEGF-A inhibition. Analysis of variance was used to compare changes in the functional abilities of three uveal melanoma cell lines following VEGF-A inhibition. A P-value < 0.05 was considered statistically significant.Results:All three cell lines produced copious amounts of VEGF-A in culture (92.1, 11785.5 ± 231.8 pg/μL; OCM-1, 4608.0 ± 324.0 pg/μL; UW-1, 8309.3 ± 634.5 pg/μL), which was reduced to undetectable levels following the administration of bevacizumab (P< 0.05). Similarly, detectable phosphorylated VEGF-R2 was present in all cells, which was reduced significantly in all cell lines following bevacizumab treatment (107525.2 ± 8602.0 versus 1024.5 ± 98.2, 46587.3 ± 4192.9 versus 12821.1 ± 1666.7, and 60394.3 ± 4026.4 versus 6908.2 ± 607.2; 92.1, OCM-1, and UW-1, respectively; P< 0.05). Of the cytokines investigated, only MMP-9 and CCL3 were ubiquitously altered across all three cell lines following bevacizumab treatment; they were upregulated (CCL3: 1072.50 ± 18.77 pg/mL versus 1281.00 ± 72.34 pg/mL; 22.5 ± 7.85 pg/mL versus 62.00 ± 9.16 pg/mL; 20.33 ± 6.35 pg/mL versus 35.00 ± 6.22 pg/mL; control versus bevacizumab; MMP-9: 25.50 ± 5.47 pg/mL versus 88.25 ± 13.38 pg/mL; 19.75 ± 4.14 pg/mL versus 45.25 ± 8.36 pg/mL; 3.25 ± 1.09 pg/mL versus 19.25 ± 3.77 pg/mL; control versus bevacizumab; 92.1, OCM-1, and UW-1, respectively; P< 0...

show abstract

Serum vascular endothelial growth factor (VEGF) levels correlate with number and location of micrometastases in a murine model of uveal melanoma

Cited by 24 publications

References 18 publications

MicroRNA-9 suppresses uveal melanoma cell migration and invasion through the NF-κB1 pathway

MicroRNA-9 suppresses uveal melanoma cell migration and invasion through the NF-κB1 pathway

Blood biomarkers of uveal melanoma metastasis

ecancermedicalscience

Contact Info

Product

Resources

About