Expression of vascular endothelial growth factor in normal epidermis, epithelial tumors and cultured keratinocytes

Abstract

Vascular endothelial growth factor (VEGF), an endothelium-specific growth factor and microvessel hypermeability factor, is expressed and secreted by several kinds of cells and is implicated in angiogenesis of tumors. The present study was performed to determine the relationship between the expression of VEGF in normal skin, benign and malignant epithelial lesions and cultured keratinocytes and the proliferative activity and degree of differentiation of keratinocytes. Skin lesions were studied immunohistochemically by staining with two anti-VEGF antibodies and secretion and production of VEGF by keratinocyte cultures were evaluated using an enzyme-linked immunosorbent assay. Low to moderate VEGF expression was observed in normal epidermis. In epithelial tumors, different reactivity patterns were observed and different areas of the same tumor expressed different amounts of VEGF. A more prominent labelling occurred in proliferative layers and/or more differentiated cells of virus-induced lesions, squamous cell carcinomas and Bowen's disease, whereas basal cell carcinomas always stained weakly for VEGF. In cultured keratinocytes, the amount of cell-associated and secreted VEGF increased with time, and the constitutively produced VEGF was mostly released extracellularly. High calcium concentrations upregulated the intracellular content of VEGF but downregulated its release. Taken together, these results showed a modulated expression and release of VEGF in relation to the stage of cell differentiation and in rapidly growing or activated keratinocytes.

Psoriasis: genetic associations and immune system changes

“…[11][12][13] A unique link between regenerative hyperplasia and inflammation may be provided by synthesis of S100 proteins (A7, A8, A9, A12) that are encoded by the epidermal differentiation complex (EDC) genes. 14 In psoriasis lesions, there is tremendous growth of the most superficial capillaries.…”

Evidence that involucrin, a marker for differentiation, is oxygen regulated in human squamous cell carcinomas

“…A possible explanation for this apparent anomaly was found in reports that VEGF and MT are expressed in oxygenated basal lamina of normal stratified epithelia and not in more differentiated, suprabasal layers farthest from the blood vessels (Quaife et al, 1994;Sundelin et al, 1997;Viac et al, 1997). This led to the conclusion that VEGF and MT are downregulated by differentiation in stratified epithelia (Quaife et al, 1994;Viac et al, 1997).…”

“…This led to the conclusion that VEGF and MT are downregulated by differentiation in stratified epithelia (Quaife et al, 1994;Viac et al, 1997). In analogy with their untransformed counterpart, squamous cell carcinomas often express markers for terminal differentiation in the centre of tumour nests farthest from blood vessels (Roland et al, 1996).…”

“…This would appear to be inconsistent with oxygen regulation. However, the transcription status of oxygen-regulated genes can be coregulated by differentiation (Webster et al, 1990;Claffey et al, 1992;Quaife et al, 1994;Levy and Kelly, 1997;Viac et al, 1997) and the effect of differentiation on involucrin expression was therefore examined by comparing its expression in moderately differentiated SCC9 and poorly differentiated SCC4 cells exposed to acute and chronic hypoxia.…”

Expression and localization of the vascular endothelial growth factor and changes of microvessel density during hair follicle development of Liaoning cashmere goats

“…The vascular endothelial growth factor (VEGF), also known as the vascular permeability factor (Viac et al, 1997), is a specific mitogen for vascular endothelial cells (VECs) (Roy et al, 2006). For normal cell growth and differentiation, an adequate supply of blood appears to be of fundamental importance in the active processes of hair growth.…”