Increased Expression of Vascular Permeability Factor (Vascular Endothelial Growth Factor) in Bullous Pemphigoid, Dermatitis Herpetiformis, and Erythema Multiforme

Brown, Lawrence F.; Harrist, Terence J.; Yeo, Kiang-Teck; Ståhle‐Bäckdahl, Mona; Jackman, Robert W.; Berse, Brygida; Tognazzi, Kathi; Dvorak, Harold F.; Detmar, Michael

doi:10.1111/1523-1747.ep12606974

Cited by 140 publications

(103 citation statements)

References 31 publications

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“…Atypically severe orf virus lesions have been reported for thermally injured skin (20), and erythema multiforme reactions are a relatively common complication of orf virus infection. Intriguingly, both of these pathologies, in the absence of orf virus, have been linked to elevated levels of VEGF (6,17).…”

Section: Discussionmentioning

confidence: 99%

Viral Vascular Endothelial Growth Factor Plays a Critical Role in Orf Virus Infection

Savory¹,

Stacker

Fleming³

et al. 2000

J Virol

125

116

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Infection by the parapoxvirus orf virus causes proliferative skin lesions in which extensive capillary proliferation and dilation are prominent histological features. This infective phenotype may be linked to a unique virus-encoded factor, a distinctive new member of the vascular endothelial growth factor (VEGF) family of molecules. We constructed a recombinant orf virus in which the VEGF-like gene was disrupted and show that inactivation of this gene resulted in the loss of three VEGF activities expressed by the parent virus: mitogenesis of vascular endothelial cells, induction of vascular permeability, and activation of VEGF receptor 2. We used the recombinant orf virus to assess the contribution of the viral VEGF to the vascular response seen during orf virus infection of skin. Our results demonstrate that the viral VEGF, while recognizing a unique profile of the known VEGF receptors (receptor 2 and neuropilin 1), is able to stimulate a striking proliferation of blood vessels in the dermis underlying the site of infection. Furthermore, the data demonstrate that the viral VEGF participates in promoting a distinctive pattern of epidermal proliferation. Loss of a functional viral VEGF resulted in lesions with markedly reduced clinical indications of infection. However, viral replication in the early stages of infection was not impaired, and only at later times did it appear that replication of the recombinant virus might be reduced.

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Section: Discussionmentioning

confidence: 99%

Viral Vascular Endothelial Growth Factor Plays a Critical Role in Orf Virus Infection

Savory¹,

Stacker

Fleming³

et al. 2000

J Virol

125

116

View full text Add to dashboard Cite

show abstract

“…Our finding of accumulation of VEGF on the vascular endothelium in the histologically normal dermis suggests that a constitutive low level VEGF expression may regulate skin vessel function under normal physiological conditions. Overexpression of VEGF has been reported in skin disorders that are characterized by angiogenesis and increased vascular permeability (Brown et al, 1995a). VEGF is strongly expressed by epidermal keratinocytes in wound healing and psoriasis, both accompanied by angiogenesis and increased microvascular permeability (Brown et al, 1992;Detmar et al, 1994).…”

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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“…Overexpression of VEGF has been found in angiogenic processes of skin; physiologically in wound healing (Brown et al, 1992), and in several pathological non-neoplastic conditions such as psoriasis (Detmar et al, 1994) and bullous diseases . These studies showed that the epidermis is the main source for VEGF production in skin.…”

Section: Introductionmentioning

confidence: 99%

VEGF/VPF overexpression in skin of transgenic mice induces angiogenesis, vascular hyperpermeability and accelerated tumor development

et al. 1998

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Increased Expression of Vascular Permeability Factor (Vascular Endothelial Growth Factor) in Bullous Pemphigoid, Dermatitis Herpetiformis, and Erythema Multiforme

Cited by 140 publications

References 31 publications

Viral Vascular Endothelial Growth Factor Plays a Critical Role in Orf Virus Infection

Viral Vascular Endothelial Growth Factor Plays a Critical Role in Orf Virus Infection

Enhanced expression of vascular endothelial growth factor in metastatic melanoma

VEGF/VPF overexpression in skin of transgenic mice induces angiogenesis, vascular hyperpermeability and accelerated tumor development

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