低氧诱导因子1α通过CX3CR1在胰腺癌嗜神经侵袭中作用
Regulation of hypoxia-inducible factor-1α on peri-neural invasion in pancreatic cancer through the chemokine receptor CX3CR1
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摘要:目的 探索低氧诱导因子1α(HIF-1α)和细胞趋化因子受体CX3CR1的相互调节在胰腺癌嗜神经侵袭方面的作用。方法 通过免疫组织化学实验, 探究在胰腺癌的组织样本中HIF-1α与CX3CR1的相互作用对嗜神经侵袭的作用; 用siRNA双链和过表达质粒沉默/过表达HIF-1α和CX3CR1基因, 然后通过Western blot免疫印迹实验检测HIF-1α、CX3CR1表达的变化。结果 在胰腺癌组织中, HIF-1α蛋白表达水平与肿瘤直径(F=7.81, P < 0.05), 淋巴结转移(r=0.24, P < 0.01), 肿瘤的病理淋巴结转移阶段(r=0.39, P < 0.05)相关; 在人类胰腺癌细胞系、胰腺癌患者手术标本中, HIF-1α和CX3CR1的表达均具有相关性, 并且与胰腺癌的嗜神经侵袭相关联。结论 HIF-1α和CX3CR1的相互作用可以调节胰腺癌的嗜神经侵袭。Abstract:Objective This study aimed to elucidate the mechanism underlying the reciprocal regulation between hypoxia-inducing factor-1α(HIF-1α) and the chemokine receptor CX3CR1 on the neural invasion of pancreatic cancer cells.Methods Immunohistochemistry was used to examine the interaction between HIF-1α and CX3CR1 in tissue specimens of pancreatic cancer, and the effect of this interaction on peri-neural invasion(PNI).Then, HIF-1α and CX3CR1 gene were knocked down or overexpressed by the construction of siRNA duplexes/ plasmids to estimate their correlation.The reciprocal regulation of HIF-1α and CX3CR1 was assessed by Western blot assay.Results HIF-1 α was involved in PNI in pancreatic cancer specimens.HIF-1α expression was correlated with clinicopathological parameters in pancreatic cancer patients.HIF-1α and CX3CR1 were correlatively expressed in human pancreatic cancer cell lines and tissue specimens, and both were associated with PNI in pancreatic cancer.Conclusion The reciprocal regulation of HIF-1α and CX3CR1 modulates the neurotropism of pancreatic cancer.
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