Induction of vascular endothelial growth factor expression by hypoxia and by glucose deficiency in multicell spheroids: implications for tumor angiogenesis.

Shweiki, Dorit; Neeman, Michal; Itin, Ahuva

doi:10.1073/pnas.92.3.768

Cited by 523 publications

(297 citation statements)

References 24 publications

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“…We also observed elevated expression of the protein phosphatase DUSP1, which is upregulated during conditions of oxidative stress and heat shock. 12 Vascular endothelial growth factor (VEGF) also participates in stress responses 13 and showed higher expression levels after overnight incubation of blood. Other known stress-response genes found to be upregulated during overnight shipment included TGF-beta-inducible early growth response gene (TIEG) and growth arrest and DNA-damage-inducible alpha (GADD45A) and beta (GADD45B).…”

Section: Resultsmentioning

confidence: 99%

Expression levels for many genes in human peripheral blood cells are highly sensitive to ex vivo incubation

et al. 2004

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Section: Resultsmentioning

confidence: 99%

Expression levels for many genes in human peripheral blood cells are highly sensitive to ex vivo incubation

et al. 2004

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“…In all xenografts, equally high levels of VEGF mRNA were found, independent of the VEGF expression in the parental cell line (Potgens et al, 1995). Similarly, in xenografted tumours in nude mice in vivo, concomitantly with invasion of new blood vessels and restoration of normoxia in the implanted tumour, VEGF expression was gradually down-regulated to a constitutive low level of expression, representing the output of non-stressed tumour cells (Shweiki et al, 1995). Expression of VEGF in our series did not correlate with the primary melanoma thickness, microvessel density or patient survival in metastatic disease; this may be a reflection of the same phenomenon when hypoxia and possibly also other factors regulate the expression of VEGF in a reversible manner.…”

Section: Discussionmentioning

confidence: 99%

Enhanced expression of vascular endothelial growth factor in metastatic melanoma

Salvén

Heikkilä²,

Joensuu³

1997

Br J Cancer

139

104

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Summary Tumour growth is dependent on angiogenesis. Vascular endothelial growth factor (VEGF) is a secreted endothelial cell-specific cytokine. VEGF is angiogenic in vivo and it also acts as a vascular permeability factor. VEGF is overexpressed in many skin disorders characterized by angiogenesis and increased vascular permeability. We Folkman, 1996). One such stimulus is vascular endothelial growth factor (VEGF), which is a secreted, dimeric 46-kDa protein active as an endothelial cellspecific mitogen and as a vascular permeability factor. VEGF expression has been detected in a large variety of malignant human tumours, and it has been concluded that VEGF has an important role in tumour biology and in the process of tumour angiogenesis (reviewed in Dvorak et al, 1995;Ferrara, 1995). VEGF mRNA has also been detected in metastatic melanoma cells in cerebral melanoma metastases (Hatva et al, 1995).Progression of melanoma is supposed to be associated with an angiogenic response, and several histological studies have shown an increase in vascular structures in malignant melanoma, which is not the case in common naevocellular naevi (reviewed in Denijn and Ruiter, 1993). Expression of VEGF in mouse VEGF cDNAtransected melanoma cells is associated with increased tumour growth, angiogenesis and experimental metastasis in vivo in a nude mouse model (Claffey et al, 1996). This suggests a role for VEGF as a positive regulatory stimulus in angiogenesis, progression and dissemination of malignant melanoma. The aim of the Received 30 October 1996 Revised 13 March 1997 Accepted 20 March 1997 Correspondence to: P Salven present study was to investigate the expression of VEGF in normal dermis, naevocellular naevi and in primary and metastatic melanoma and to study the relationship between VEGF expression and tumour microvessel density, patient survival and other clinicopathological variables. MATERIALS AND METHODS Patients and tissue samplesThe study includes six patients with a common naevocellular naevus and 55 randomly selected patients with histologically diagnosed malignant melanoma treated with surgery and chemotherapy or chemoimmunotherapy in Helsinki University Central Hospital, during the time period from 1989 to 1995. The prognostic significance of VEGF expression was investigated in a series of 33 patients with a lymph node metastasis from malignant melanoma. Twenty of the patients with metastatic melanoma were male and 13 were female; age at the time of surgery ranged from 30 to 84 years (median 56 years). All patients with metastatic disease were followed up until death or for at least 4 years, as calculated from the surgical removal of the lymph node metastasis. The overall 2-year survival was 35% and 4-year survival 24%.Determination of VEGF expression VEGF expression was determined using a mouse monoclonal antihuman VEGF antibody (MAB293, IgG2b, R&D Research, MN, USA) raised against the 165 amino acid species of the polypeptide. The 5-,um frozen sections were rehydrated, incubated for 30 min in 0.3% hydrogen...

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“…In contrast to the previous smaller series (Stockhammer et al, 2000), we found a strong correlation of VEGF with CSF lactate and a less stronger correlation with CSF albumin. The correlation with CSF lactate makes sense in that lactate may reflect the metabolism of tumour cells in a low-oxygen environment which in turn induces VEGF expression in tumour cells (Shweiki et al, 1995;Fukumura et al, 2001;Ziemer et al, 2001). In fact, acidic pH itself induces VEGF expression (Fukumura et al, 2001).…”

Section: Discussionmentioning

confidence: 99%

Vascular endothelial growth factor (VEGF) in leptomeningeal metastasis: diagnostic and prognostic value

et al. 2004

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This study examined the diagnostic and prognostic value of vascular endothelial growth factor (VEGF) levels in the cerebrospinal fluid (CSF) of 39 patients with leptomeningeal metastasis (LM). Vascular endothelial growth factor levels at diagnosis were significantly higher in patients with LM (median 359 pg ml À1 ) than in patients with other neurological diseases (median o25 pg ml À1 ). The specificity of VEGF levels above 250 pg ml À1 for LM was high (98.3%), while the sensitivity was low (51.4%; 73% for VEGF values above 100 pg ml À1 ). In 49% of the LM patients, particularly with lymphoma or medulloblastoma, VEGF levels were below 250 pg ml À1 and thus in the range of VEGF levels in other neurological diseases. Vascular endothelial growth factor levels correlated significantly with CSF lactate and albumin. Vascular endothelial growth factor levels mirrored the clinical course with a marked reduction in response to therapy and an increase at relapse in some patients who had serial CSF samples available. Multivariate Cox regression analysis showed VEGF below 100 pg ml À1 (relative risk (RR) ¼ 4.24, P ¼ 0.0002) and age below 60 years (RR ¼ 2.5, P ¼ 0.004) to be associated with longer survival in LM. In conclusion, CSF VEGF levels in LM vary considerably. High VEGF levels have a very high specifity for LM and may help to establish the diagnosis. The role of VEGF as a predictor of outcome should be substantiated in prospective studies.

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Induction of vascular endothelial growth factor expression by hypoxia and by glucose deficiency in multicell spheroids: implications for tumor angiogenesis.

Cited by 523 publications

References 24 publications

Expression levels for many genes in human peripheral blood cells are highly sensitive to ex vivo incubation

Expression levels for many genes in human peripheral blood cells are highly sensitive to ex vivo incubation

Enhanced expression of vascular endothelial growth factor in metastatic melanoma

Vascular endothelial growth factor (VEGF) in leptomeningeal metastasis: diagnostic and prognostic value

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