Expression and function of vascular endothelial growth factor receptor-1 on human colorectal cancer cells

Fan, Fan; Wey, Jane; McCarty, Marya F.; Belcheva, A.; Liu, Wenbiao; Bauer, Todd W.; Somcio, Ray; Wu, Yan; Hooper, Andrea T.; Hicklin, Daniel J.; Ellis, Lee M.

doi:10.1038/sj.onc.1208246

Cited by 309 publications

(228 citation statements)

References 34 publications

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“…PLGF-1-induced RPE cell permeability involves the MEK/ ERK signalling pathway A recent publication shows that in human colorectal cancer cells, VEGFR-1-induced motility involves ERK1/2 activation [20].…”

Section: Resultsmentioning

confidence: 99%

Placental growth factor-1 and epithelial haemato–retinal barrier breakdown: potential implication in the pathogenesis of diabetic retinopathy

et al. 2006

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Aims/hypothesis Disruption of the retinal pigment epithelial (RPE) barrier contributes to sub-retinal fluid and retinal oedema as observed in diabetic retinopathy. High placental growth factor (PLGF) vitreous levels have been found in diabetic patients. This work aimed to elucidate the influence of PLGF-1 on a human RPE cell line (ARPE-19) barrier in vitro and on normal rat eyes in vivo. Methods ARPE-19 permeability was measured using transepithelial resistance and inulin flux under stimulation of PLGF-1, vascular endothelial growth factor (VEGF)-E and VEGF165. Using RT-PCR, we evaluated the effect of hypoxic conditions or insulin on transepithelial resistance and on PLGF-1 and VEGF receptors. The involvement of mitogen-activated protein kinase kinase (MEK)/extracellular signal-regulated kinase (ERK, also known as EPHB2) signalling pathways under PLGF-1 stimulation was evaluated by western blot analysis and specific inhibitors. The effect of PLGF-1 on the external haemato-retinal barrier was evaluated after intravitreous injection of PLGF-1 in the rat eye; evaluation was by semi-thin analysis and zonula occludens-1 immunolocalisation on flat-mounted RPE. Results In vitro, PLGF-1 induced a reversible decrease of transepithelial resistance and enhanced tritiated inulin flux. These effects were specifically abolished by an antisense oligonucleotide directed at VEGF receptor 1. Exposure of ARPE-19 cells to hypoxic conditions or to insulin induced an upregulation of PLGF-1 expression along with increased transcellular permeability. The PLGF-1-induced RPE cell permeability involved the MEK signalling pathway. Injection of PLGF-1 into the rat eye vitreous induced an opening of the RPE tight junctions with subsequent sub-retinal fluid accumulation, retinal oedema and cytoplasmic translocation of junction proteins. Conclusions/interpretation Our results indicate that PLGF-1 may be a potential regulation target for the control of diabetic retinal and macular oedema.

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Section: Resultsmentioning

confidence: 99%

Placental growth factor-1 and epithelial haemato–retinal barrier breakdown: potential implication in the pathogenesis of diabetic retinopathy

et al. 2006

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“…In general, the metastatic pathway in gastric cancer is not haematogenous, and therefore, the responsible cells expressing VEGFR1 may be monocytes and not HPCs and CECs. A last possibility is that VEGFR1 originates from circulating cancer cells in the bone marrow or peripheral blood (Fan et al, 2005;Yang et al, 2006). However, the number of circulating cancer cells is very low, which allow us to ignore the possibility that cancer cell are the origin of VEGFR1 expression.…”

Section: Discussionmentioning

confidence: 99%

Identification of the high-risk group for metastasis of gastric cancer cases by vascular endothelial growth factor receptor-1 overexpression in peripheral blood

et al. 2007

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Identification of an isolated tumour cell with metastatic ability is important for predicting the recurrence and prognosis of gastric cancer. A biological marker for evaluating the metastatic ability of gastric cancer cells has not yet been identified. We assessed vascular endothelial growth factor receptor-1 mRNA expression by quantitative real-time reverse transcriptase-polymerase chain reaction. Vascular endothelial growth factor receptor-1 mRNA in peripheral blood was more highly expressed in perioperative metastasis-positive and postoperative recurrence cases than in normal control cases, early cancer cases and nonmetastatic advanced cancer cases. The peripheral blood vascular endothelial growth factor receptor-1 mRNA-positive group was associated with advanced clinical stage, deep invasion beyond the muscularis propria, lymphatic involvement, vascular involvement, lymph node metastasis, positive peritoneal lavage cytology, preoperative metastasis and postoperative recurrence. Flow cytometry analysis disclosed that vascular endothelial growth factor receptor-1 expressing cells in the peripheral blood were more abundant in cancer cases with metastases than in cases without metastases. Our data suggest that the amount of positive cells may provide information on the clinical features of gastric cancer, especially in regard to gastric cancer metastasis.

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“…The potential pleiotropic effects of anti-VEGF therapy is in part due to the fact that VEGF receptors are expressed not only on endothelial cells in tumors, but also on subsets of hematopoietic cells, stromal cells, in addition to malignant cells in certain human cancers (e.g. breast, brain, colorectal and pancreatic [11,[38][39][40]). The existing clinical data on the mechanisms of action of anti-VEGF therapy that have been suggested by preclinical studies [9,11,12] are discussed below.…”

Section: Mechanisms Of Actionmentioning

confidence: 99%

VEGF-targeted cancer therapy strategies: current progress, hurdles and future prospects

Duda

Batchelor

Willett

et al. 2007

Trends in Molecular Medicine

123

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Despite setbacks, the clinical development of antiangiogenic agents has accelerated remarkably over the past 3-4 years. Consequently, there are currently three direct inhibitors of the VEGF pathway approved for use in cancer therapy. Other agents that block the VEGF pathway are in advanced stages of clinical development and have shown promising results. With these exciting developments come crucial questions regarding the use of these new molecular-targeted agents, alone or in combination with standard cytotoxic or targeted agents. Importantly, the mechanisms of action of anti-VEGF therapy remain unknown. Here, we discuss several potential mechanisms of action such as tumor vascular normalization, bone marrow-derived cell recruitment blockade and cytostatic effects of anti-VEGF therapy. We review the current progress, the major stumbling blocks and the future directions for anti-cancer therapy using anti-VEGF agents, emphasizing clarification of the underlying molecular mechanisms of action and biomarker identification and validation.

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Expression and function of vascular endothelial growth factor receptor-1 on human colorectal cancer cells

Cited by 309 publications

References 34 publications

Placental growth factor-1 and epithelial haemato–retinal barrier breakdown: potential implication in the pathogenesis of diabetic retinopathy

Placental growth factor-1 and epithelial haemato–retinal barrier breakdown: potential implication in the pathogenesis of diabetic retinopathy

Identification of the high-risk group for metastasis of gastric cancer cases by vascular endothelial growth factor receptor-1 overexpression in peripheral blood

VEGF-targeted cancer therapy strategies: current progress, hurdles and future prospects

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