[Upregulation of the Chemokine Receptor CCR7 expression by HIF-1alpha and HIF-2alpha in non-small cell lung cancer.].
BACKGROUND
CCR7 is closely related with the lymph node metastasis of non-small cell lung cancer. The objective of this work is to investigate the expressions of chemokine receptor CCR7, hypoxia inducible factor 1alpha (HIF-1alpha) and hypoxia inducible factor 2alpha (HIF-2alpha) protein in non small cell lung cancer and the relationships of their expression, and to study the mechanism of CCR7 upregulation in NSCLC.


METHODS
T he levels of expressions of CCR7, HIF-1alpha and HIF-2alpha protein were detected in 94 specimens of human primary non small cell lung cancer by immunohistochemical S-P method. Human lung adenocarcinoma cell line A549 cells were transfected by lipofection with HIF-1alpha siRNA, HIF-2alpha siRNA, the change of CCR7 was observed by RT-PCR and immunofluorescence staining. Correlations between the expression of CCR7 and HIF-1alpha, HIF-2alpha were respectively analyzed.


RESULTS
Immunohistochemistry showed that CCR7 was distributed in cytoplasm and/or membrane of tumor cells, HIF-1alpha, HIF-2alpha was distributed in nucleus and/or cytoplasm of tumor cells. The levels of expressions of CCR7, HIF-1alpha and HIF-2alpha protein were found to be 75.53% (71/94), 54.25% (51/ 94) and 70.21% (66/94) in non small cell lung cancer, respectively. the levels of expression of CCR7 protein were closely related to the clinical stages (P <0.001) and lymph node metastasis (P <0.001) of non small cell lung cancer, but there was no correlation with age, gender, histology (P >0.05). Furthermore, A significant correlation were found among CCR7, Hif-1alpha and HIF-2alpha (r =0.272, P <0.01) (r =0.225, P <0.05). In addition, the expression of CCR7 mRNA and protein levels were decreased in the transfected specific HIF-1alpha, HIF-2alpha siRNA group (P <0.05).


CONCLUSIONS
CCR7 expression is significantly associated with non small cell lung cancer invasion and metastasis. The upregulation of CCR7 is regulated by HIF-1alpha and HIF-2alpha in non small cell lung cancer.
Li
Yang
Y
Department of Pathology, College of Basic Medical Sciences, China Medical University and Department of Pathology, the First Affiliated Hospital of China Medical University, Shenyang, 110001, China.
Zhang
Qingfu
Q
Jiang
Lili
L
Qiu
Xueshan
X
Wang
Enhua
E