VASCULAR ENDOTHELIAL GROWTH-FACTOR PRODUCTION IN NORMAL EPIDERMIS ANDIN BENIGN AND MALIGNANT EPITHELIAL SKIN TUMORS

Vascular endothelial growth factor (VEGF) increases vascular permeabil ity and acts as a mitogen for endothelial cells in vivo and in vitro. We and others recently demonstrated that cultured human keratinocytes constitutively secrete VEGF. In the present study, we examined the exp ression of this growth factor in various epithelial skin tumors and in normal skin. Using in situ hybridization, we detected strong VEGF mRN A expression in all of 10 squamous cell carcinomas, 13 common warts, 1 1 seborrheic keratoses, and in 7 of 8 keratoacanthomas studied. By con trast, we found no VEGF mRNA in 9 of 14 basal cell carcinomas. VEGF mR NA was readily detectable within the epidermis adjacent to the tumors as well as in tumor cells and in the epidermis of normal human skin. N orthern hybridization of RNA derived from normal human epidermis ident ified VEGF transcripts of 3.7 and 1.8 kb, and reverse transcriptase po lymerase chain reaction confirmed that epidermal cells, like keratinoc ytes in vitro, express the three major splice forms of VEGF. Immunohis tochemical staining with monoclonal antibodies confirmed that expressi on of VEGF mRNA was accompanied by the presence of VEGF protein. Our d ata demonstrate that VEGF production by tumor cells in situ does not d istinguish malignant from benign epithelial tumors of the skin because it is present in both. The constitutive expression of VEGF by normal keratinocytes in situ suggests that this angiotropic cytokine is impor tant for the regulation of vessel function under physiologic condition s.