CCR1 knockdown suppresses human non-small cell lung cancer cell invasion.
OBJECTIVE
CC chemokine receptor 1 (CCR1) plays a critical role in the recruitment of leukocytes to the site of inflammation. Tumor invasion and metastasis share many similarities with leukocyte trafficking, which is critically regulated by chemokines and their receptors. In this study, we aimed to assess the role of CCR1 in non-small cell lung cancer (NSCLC).


METHODS
CCR1 expression was determined by Western blotting in two human NSCLC clones (95C and 95D) with different metastatic potential. We silenced CCR1 expression through microRNA-mediated RNA interference, and examined the invasiveness and proliferation of CCR1-silenced NSCLC cell through Matrigel assay and MTT assay. Matrix metalloproteinases (MMPs) activity was determined by gelatin zymography.


RESULTS
We found that expression of CCR1 was correlated with the aggressive phenotype of the NSCLC cells. CCR1 knockdown significantly suppressed the invasiveness of NSCLC cells, but had only a minor effect on cell proliferation. Moreover, we demonstrated that CCR1 knockdown significantly reduced the expression level of matrix metalloproteinase-9.


CONCLUSIONS
These findings suggest that CCR1 contributes to NSCLC cell migration by stimulating cell invasion, independent of cell proliferation. CCR1 might be a new target for NSCLC therapy.
Wang
Chang-Li
CL
Tianjin Lung Cancer Center, Tianjin, China.
Sun
Bing-Sheng
BS
Tang
Yong
Y
Zhuang
Hong-Qing
HQ
Cao
Wei-Zhi
WZ
D001483:Base Sequence; D002289:Carcinoma, Non-Small-Cell Lung / Q000235:genetics* / Q000473:pathology*; D002455:Cell Division; D045744:Cell Line, Tumor; D002465:Cell Movement; D015536:Down-Regulation; D020868:Gene Silencing; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics* / Q000473:pathology*; D020782:Matrix Metalloproteinases / Q000378:metabolism; D035683:MicroRNAs / Q000235:genetics; D008969:Molecular Sequence Data; D009361:Neoplasm Invasiveness / Q000235:genetics* / Q000473:pathology; D009362:Neoplasm Metastasis / Q000235:genetics / Q000473:pathology; D010641:Phenotype; D034622:RNA Interference; D012334:RNA, Neoplasm / Q000235:genetics; D054389:Receptors, CCR1 / Q000235:genetics*
C515300:CCR1 protein, human; D035683:MicroRNAs; D012334:RNA, Neoplasm; D054389:Receptors, CCR1; D020782:Matrix Metalloproteinases