C‑C chemokine receptor type 2 promotes epithelial‑to‑mesenchymal transition by upregulating matrix metalloproteinase‑2 in human liver cancer

Li,Huijin; Li,Hui; Li,Xiao‑Peng; Zou,Haojun; Liu,Liting; Liu,Wangqiao; Duan,Tao

doi:10.3892/or.2018.6660

C‑C chemokine receptor type 2 promotes epithelial‑to‑mesenchymal transition by upregulating matrix metalloproteinase‑2 in human liver cancer

Authors:
- Huijin Li
- Hui Li
- Xiao‑Peng Li
- Haojun Zou
- Liting Liu
- Wangqiao Liu
- Tao Duan
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Affiliations: Department of General Surgery, The Second People's Hospital of Changzhi, Changzhi, Shanxi 046011, P.R. China, Department of Dermatology, The Second People's Hospital of Changzhi, Changzhi, Shanxi 046011, P.R. China, Shaanxi Normal University General Publishing House Co., Ltd., Xi'an, Shaanxi 710062, P.R. China, Department of Ophthalmology, The Second People's Hospital of Changzhi, Changzhi, Shanxi 046011, P.R. China
Published online on: August 17, 2018 https://doi.org/10.3892/or.2018.6660
Pages: 2734-2741

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Abstract

C‑C chemokine receptor type 2 (CCR2) is aberrantly expressed in a variety of tumor cells, and participates in the regulation of tumor cell progression, metastasis and immune escape. However, the mechanism of action of CCR2 in liver cancer remains unclear. In the present study, the aim was to elucidate the molecular mechanism underlying the regulation of epithelial‑to‑mesenchymal transition (EMT) by CCR2 in liver cancer cells. Initially, CCR2 expression in liver cancer tissues was measured, and the survival time of patients was analyzed by Kaplan‑Meier analysis. In liver cancer cells, the mRNA and protein expression levels of CCR2, matrix metalloproteinase‑2 (MMP2), E‑cadherin and vimentin were evaluated by reverse transcription‑quantitative polymerase chain reaction and western blotting. Cell viability, migration and invasion were determined by Cell Counting Kit‑8, wound healing and Transwell chamber assays, respectively. Additionally, the binding between CCR2 and MMP2 was identified by co‑immunoprecipitation (Co‑IP). It was observed that CCR2 was abnormally upregulated in liver cancer tissues and significantly associated with the tumor diameter, metastasis and stage. The survival of patients with high CCR2 expression was lower compared with that of patients with low CCR2 expression. In addition, the number of cells that penetrated the transwell chamber membrane was significantly reduced following treatment with CCR2‑small interfering RNA (siRNA). Furthermore, CCR2 was found to participate in MMP2‑induced EMT, while CCR2‑siRNA transfection reduced the expression and activity of MMP2, and confirmed the specific binding between CCR2 and MMP2. Co‑IP also identified the independent interaction between endogenous proteins in HepG2 cells. These results revealed that CCR2 promotes EMT in liver cancer. Thus, CCR2 is an attractive novel target for inhibiting invasion and metastasis of liver cancer cells.

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