Expression of HIF-1α and HIF-2α in small cell lung cancer stem cells and tissues and their significance / 临床与实验病理学杂志

ABSTRACT

Purpose To observe the expression of HIF-1αand HIF-2α in tumor stem cells and tumor tissues of small cell lung cancer (SCLC) and to explore their clinical significance.Methods The defined serum-free culture was used to enrich the third passage tumor spheres cells from H446 as the tumor stem cells.Real-time PCR was performed to determine the mR-NA expression level of HIF-1α and HIF-2α in H446 tumor stem cells.Immunofluorescence staining was performed to determine the protein expression level of HIF-1α and HIF-2α in H446 tumor stem cells.Immunohistochemistry SP method was used to detect the expression of HIF-1α and HIF-2αt in SCLC tissues.Results The mRNA expression level of HIF-2α was up-regulated in tumor stem cells.However,the mRNA expression level of HIF-1 α was down-regulated in tumor stem cells (P ＜ 0.05).The expression of HIF-2α protein was positive in tumor stem cells.In contrast,HIF-1α protein was negative in tumor stem cells.In SCLC tissues,the positive rate of HIF-1α was 46.7％ (28/60),and the positive rate of HIF-2α was 25％ (15/60).Correlation analysis showed that HIF-2α was positively correlated with SCLC stem cell marker uPAR,and they co-localized around necrotic regions.The expression of HIF-2α was closely related to tumor diameter and distant metastasis.In contrast,the expression of HIF-1α had no relationship with age,sexy,tumor size,lymph metastasis,pleural invasion and distant metastasis (P ＞ 0.05).Conclusion HIF-2α is up-regulated in SCLC stem cells and positively correlated with SCLC stem cell marker uPAR,which are associated with the tumor diameter and distant metastasis of SCLC patients,suggesting that the expression of HIF-2α may be related to SCLC stem-like characteristics.