Survival of salivary pleomorphic adenoma cells in hypoxic condition

涎腺多形性腺瘤(PA)的组织病理学特征是具有多彩的间质和黏液样外观，血管稀少，PA细胞被认为能够在低氧条件下生存。为了了解低氧依赖的细胞增殖方式，我们检测了低氧诱导因子1α(α)、血管内皮生长因子和降解低氧诱导因子1α的von Hippel-Lindau的蛋白和基因表达水平。从人腮腺多形性腺瘤中建立的SM-AP细胞表现出更高的HIF-1α表达水平，并且在低氧条件下其表达水平保持在高于有氧条件下。SM-AP细胞VHL基因表达水平较低。同样，移植的SM-AP细胞的肿瘤组织质量在O2浓度下低于正常皮下组织。结果表明，多形性腺瘤细胞可以在低氧条件下增殖，维持较高水平的HIF-1α蛋白，因为较低的α蛋白水平抑制了HIF-1蛋白的降解。因此，低氧更有利于PA细胞的增殖。

Salivary pleomorphic adenoma(PA) is histopathologically characaterized by its colorful stroma with myxoid appearances, which are poorly vascularized, and PA cells are supposed to be able 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), which degrades HIF-1α. SM-AP cells, which I established from a human parotid pleomorphic adenoma, showed more enhanced levels of HIF-1α, and their VEGF protein levels were kept higher in hypoxic conditions than in aerobic ones. SM-AP cells showed lower expression levels for the vHL gene. Likewise, tumor tissue masses of transplanted SM-AP cells were lower in O_2 concentration than normal subcutanous tissue. The results indicate that pleomorphic adenoma cells can proliferate in the hypoxic condition in which HIF-1αprotein levels were maintained in higher levels because the degradation of HIF-1αwas inhibited due to the lower vHL protein levels. It is thus concluded that hypoxia is more beneficial for PA cell proliferation.