Atypical chemokine receptor D6 inhibits human non-small cell lung cancer growth by sequestration of chemokines.
Chemokines and their receptors have been shown to play a vital role in lung cancer progression. D6 is an atypical chemokine receptor which is able to internalize and degrade chemokines. To investigate the potential role of D6 in lung cancer, we established D6-overexpressing A549 lung cancer cell lines by the transfection of human D6 cDNA. Results showed that D6 inhibited the proliferation of cancer cellsin vitroand tumorigenesisin vivo. We also determined chemokine levels in the supernatant and showed that a number of chemokines (CCL2/4/5) had significantly decreased protein levels in D6-overexpressing cells compared with the controls, whereas no significant changes in mRNA expression levels of these chemokines were detected. The cell cycle distribution and expression of certain growth factors and their receptors did not change in the D6-overexpressing cells compared with parental cells. Thus, our results suggest that D6 is a negative regulator of growth in lung cancer, mainly by the sequestration of specific chemokines.
Central Laboratory of Oncology, Tongji University School of Medicine, Shanghai 200433, P.R. China.
Feng Ying
FY
Wu
Jiang
J
Fan
Liang
L
Tang
Yin Min
YM
Zhao
Cai Cun
CC
Zhou
D6; chemokines; decoy receptor; lung neoplasm; proliferation