Survival of salivary pleomorphic adenoma cells in hypoxic condition

涎腺多形性腺瘤的组织病理学特征是其间质色彩鲜艳，其中黏液样间质血运较差。多形性腺瘤(PA)细胞嵌在这种血管稀少的间质中，被认为有自己的装置在低氧条件下生存。为了了解细胞增殖的低氧依赖方式，我们检测了多形性腺瘤来源的SM-AP细胞中低氧诱导因子1α、血管内皮生长因子和降解低氧诱导因子1α的von Hippel-Lindau蛋白的蛋白和基因表达水平。在低氧条件下，血管内皮生长因子的基因表达水平更高，而缺氧诱导因子-1α的基因表达水平没有明显提高。相反，缺氧条件下的缺氧诱导因子-1α和血管内皮生长因子蛋白水平高于有氧条件下的水平。SM-AP细胞VHL基因表达水平较低。一方面，低氧条件下血管内皮细胞生长因子蛋白水平低于有氧状态。结果表明，PA细胞能够在低氧条件下增殖，这可能是由于HIF-1α的积聚，可能是由于抑制了VHL的水平。

Salivary pleomorphic adenoma is histopathologically characaterized by its colorful stroma including myxoid one which is poorly vascularized. Pleomorphic adenoma (PA) cells embedded in such poorly-vasculaized stromata are supposed to have their own device to survive in hypoxic conditions. To understand the hypoxia-dependent manner of cellular proliferation, we determined both protein and gene expression levels of hypoxia-inducible factor 1α (HIF-1α), vascular endothelial growth factor (VEGF), and von Hippel-Lindau (vHL) protein which degrades HIF-1α in SM-AP cells originated from a pleomorphic adenoma. They showed more enhanced gene expression levels for VEGF but not for those for HIF-1α under hypoxic conditions. In contrast, HIF-1α and VEGF protein levels were kept higher in hypoxic conditions than in aerobic ones. SM-AP cells had lower expression levels for the vHL gene. On the one hand, their VEGF protein levels were kept lower in hypoxic conditions than in aerobic ones. The results indicate that PA cells are able to proliferate in the hypoxic condition because of the accumulation of HIF-1α probably due to repressed levels of vHL.