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The human chemokine receptor CCRL2 suppresses chemotaxis and invasion by blocking CCL2-induced phosphorylation of p38 MAPK in human breast cancer cells

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Abstract

The human chemokine receptor CCRL2 is a member of the atypical chemokine receptor family. CCRL2 is unable to couple with G-proteins and fails to induce classical chemokine signaling for the highly conserved DRYLAIV motif essential for signaling has been changed to QRYLVFL. We investigated whether CCRL2 is involved in the chemotaxis, invasion, and proliferation of human breast cancer cells. Firstly, expression of CCRL2 was determined in six breast cancer cell lines by real-time RT-PCR and Western blot. Then, we established stable cell lines overexpressing CCRL2 to explore the function of CCRL2 in chemotaxis and invasion by transwell assays, and the signaling downstream was further investigated. The effect of CCRL2 on proliferation was detected by colony formation assays and tumor xenograft study. We found that stable overexpression of CCRL2 in MDA-MB-231 and BT-549 cells attenuated the chemotaxis and invasion stimulated by its ligand CCL2. CCRL2 inhibits p38 MAPK (p38) phosphorylation and up-regulates the expression of E-cadherin. This effect was eliminated by the inhibitor of p38 MAPK. CCRL2 inhibited the growth of breast cancer cells in vitro and in vivo. Our results suggest that CCRL2 functions as a tumor suppressor in human breast cancer cells.

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    Authors and Affiliations

    1. Department of Medical Oncology, Fudan University Shanghai Cancer Center, 270 Dongan Road, Shanghai, China

      Lei-Ping Wang, Jun Cao, Jian Zhang, Bi-Yun Wang, Xi-Chun Hu & Zhong-Hua Wang

    2. Department of Breast Surgery, Fudan University Shanghai Cancer Center, 270 Dongan Road, Shanghai, China

      Zhi-Min Shao & Zhou-Luo Ou

    3. Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China

      Lei-Ping Wang, Jun Cao, Jian Zhang, Bi-Yun Wang, Xi-Chun Hu, Zhi-Min Shao, Zhong-Hua Wang & Zhou-Luo Ou

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    1. Lei-Ping Wang
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    Zhong-Hua Wang and Zhou-Luo Ou have contributed equally to this work.

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    Wang, LP., Cao, J., Zhang, J. et al. The human chemokine receptor CCRL2 suppresses chemotaxis and invasion by blocking CCL2-induced phosphorylation of p38 MAPK in human breast cancer cells. Med Oncol 32, 254 (2015). https://doi.org/10.1007/s12032-015-0696-6

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