血管内皮生长因子(VascularendothelialgrowthfactorVEGF)是一种由疏键连接的同源二聚体糖蛋白,分子量34~50KD,人VEGF基因位于染色体6p2113,由8个内显子和7个内含子构成,由于剪切方式不同可产生不同单体。VEGF广泛分布于肿瘤细胞。但VEGF受体几乎只分布于内皮细胞表面,目前已发现的VEGF受体有flt21和KDR/fik21,均属酪氨酸激酶受体[24]。VEGF与受体结合后,受体发生自身磷酸化,诱导一系列信号转导机制,从而发挥生物学效应。VEGF可增加微血管通透性,诱导血管大分子物质的漏出,有利于外基质的形成,为血管内皮细胞的增生、血管的形成、提供支持辅助血管生成。还可以通过内皮细胞特异性受体刺激血管内皮细胞增生和毛细血管袢形成,诱导血管内有丝分裂,直接刺激血管生成,并产生纤维蛋白原激活物和胶原酶,促使细胞脱落进入血管或向邻近纤维蛋白和结缔组织基质扩散,为肿瘤浸润、转移创造条件。
VEGF在涎腺粘液表皮样癌中表达主要位于中间细胞和表皮样细胞的胞浆和胞膜,它可促进血管内皮细胞增殖,刺激血管生成。因此,VEGF在病理性生长过程中起到重要作用。血管生长抑制剂,现在被认为是抑制肿瘤生长最有前途的治疗策略之一。故检测VEGF在涎腺粘液表皮样癌的表达,有助于判断肿瘤的恶性程度和病人的预后[25]。综上所述,随着肿瘤分子生物学进展,人们已认识到肿瘤的发生是一个多基因参与、多阶段的病理过程。通过研究,各种标志物对涎腺粘液表皮样癌的早期筛查、诊断、病理分型、分级、风险评估、转移趋势及预后等方面的意义各不相同[26]。所以建议这些标志物应联合应用,才能对治疗涎腺粘液表皮样癌提供科学依据。
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