Expression Of Vascular Endothelial Growth Factor Receptor-2 In The Tissue Of Patients With Basal Cell Carcinomas

[Research Background]Vascular endothelial growth factor (VEGF) is a family of growth factors, including VEGF-A, -B, -C, -D, and -E, and placental growth factor (P1GF). VEGF has been studied extensively for its angiogenic behavior in physiological and pathological conditions^[1-3].VEGF-A, also named VEGF, is considered as the most important factor in VEGF family. According to the different slicing pattern during VEGF transcription course, there are some different VEGF isotypes including VEGF₁₂₁,VEGF_l65,VEGF₁₈₉^[1].VEGF family induce the proliferation of endothelial cells, promote angiogenesis and enhance the vascular permeability by binding to VEGF receptors^[3,4]. Vascular endothelial growth factor (VEGF) plays an important role in normal and pathological angiogenesis. VEGF receptors (VEGFRs, including VEGFR-1, VEGFR-2, and VEGFR-3) and neuropilins (NRPs, including NRP-1 and NRP-2) are high-affinity receptors for VEGF and are typically considered to be specific for endothelial cells. VEGFRs belong to the receptor tyrosine kinase (RTK) family and have a characteristic structure with 7 Ig-like domains in the extracellular domain and acytoplasmic tyrosine kinase domain with a long kinase insert region. VEGF also interacts with neuropilins (NRPs), a family of non-tyrosine kinase transmembrane receptors with a small cytoplasmic domain and multiple extracellular domains. Vascular endothelial growth factor receptor-2 is the major receptor for endothelial cell function^[5,.6] Recently, VEGF receptors were found to be expressed not only on the endothelial cells but also on some non-endothelial cells^[7,10], such as hematopoietic stem cells, neuronal cells, retinal progenitor cells, as well as in some tumor cells. In our lab, we ever detected the expression of vascular endothelial growth factor receptor-1 and vascular endothelial growth factor receptor-2 on normal keratinocytes, hair follicles, and sebaceous glands, and we found that the expression of VEGFR-1 and vascular endothelial growth factor receptor-2 on psoriatic keratinocytes were elevated^[11]. The angiogenesis of tumour is the significant mechanisms in promoting tumorous growth and metastasis. So, the relationship of VEGF, VEGFR and the angiogenesis of cutaneous tumor is more and more interested. The expression of vascular endothelial growth factor receptor-2 in the tissue of patients with malignant melanoma is discovered by Lin EY et al^[12]. However, there is no research about the expression of vascular endothelial growth factor receptor-2 in the tissue of patients with basal cell carcinomas(BCC) up to now. Confirmation of the expression of vascular endothelial growth factor receptor-2 in the tissue of basal cell carcinomas will be contributed to the investigation of the biology of them in basal cell carcinomas.[Objective]To determine the expression of vascular endothelial growth factor receptor-2 in the tissue of patients with basal cell carcinomas.[Materials and Methods]We compiled 7 case of BCC that were definited by clinic and pathology. At same time, the control was normal skin tissue which was cut in the out-patient clinicoperation of our department. RT-PCR assay was employed to determine the mRNA expression of vascular endothelial growth factor receptor-2 in the tissue of patients with basal cell carcinomas. Immunofluorescence and Western Blotting techniques were used to determine the protein expression of the vascular endothelial growth factor receptor-2 in the tissue of patients with basal cell carcinomas.[Results]1. RT-PCR: mRNA expression of vascular endothelial growth factor receptor-2 could be find both in the tissue of patients with basal cell carcinomas and normal controls by RT-PCR assay. But the level of the mRNA expression of vascular endothelial growth factor receptor-2 in the former was statistically significantly higher than the latter (P＜0.001).2. Western-blot: The protein expression of vascular endothelial growth factor receptor-2 in the tissue of patients with basal cell carcinomas was also significantly higher than that in the tissue of normal controls detected by Western blotting as the same as the consequence of RT-PCR.3. Immunofluorescence: The protein expression of vascular endothelial growth factor receptor-2 was positively expressed in all layers of the epidermis in the tissue of patients with basal cell carcinomas except the stratum corneum detected by Immunofluorescence. In the normal skin, the protein of vascular endothelial growth factor receptor-2 was detected in the stratum basale and adjacent stratum spinosum. The mainly expression of vascular endothelial growth factor receptor-2 was detected on cellular membrane.[Conclusions]The significantly increased expression of vascular endothelial growth factor receptor-2 may contribute to abnormal cell proliferation in the tissue of patients with basal cell carcinomas.