The human chemokine receptor CCRL2 suppresses chemotaxis and invasion by blocking CCL2-induced phosphorylation of p38 MAPK in human breast cancer cells.
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.
Department of Medical Oncology, Fudan University Shanghai Cancer Center, 270 Dongan Road, Shanghai, China.|Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China.
Lei-Ping
LP
Wang
Department of Medical Oncology, Fudan University Shanghai Cancer Center, 270 Dongan Road, Shanghai, China.|Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China.
Jun
J
Cao
Department of Medical Oncology, Fudan University Shanghai Cancer Center, 270 Dongan Road, Shanghai, China.|Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China.
Jian
J
Zhang
Department of Medical Oncology, Fudan University Shanghai Cancer Center, 270 Dongan Road, Shanghai, China.|Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China.
Bi-Yun
BY
Wang
Department of Medical Oncology, Fudan University Shanghai Cancer Center, 270 Dongan Road, Shanghai, China.|Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China.
Xi-Chun
XC
Hu
Department of Breast Surgery, Fudan University Shanghai Cancer Center, 270 Dongan Road, Shanghai, China.|Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China.
Zhi-Min
ZM
Shao
Department of Medical Oncology, Fudan University Shanghai Cancer Center, 270 Dongan Road, Shanghai, China. wzzhuaw_2015@126.com.|Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China. wzzhuaw_2015@126.com.
Zhong-Hua
ZH
Wang
Department of Breast Surgery, Fudan University Shanghai Cancer Center, 270 Dongan Road, Shanghai, China. wzzhuaw@163.com.|Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China. wzzhuaw@163.com.
Zhou-Luo
ZL
Ou
D001943:Breast Neoplasms / Q000378:metabolism* / Q000473:pathology; D045744:Cell Line, Tumor; D018932:Chemokine CCL2 / Q000037:antagonists & inhibitors / Q000378:metabolism*; D002633:Chemotaxis / Q000502:physiology*; D005260:Female; D006801:Humans; D061986:MCF-7 Cells; D009361:Neoplasm Invasiveness / Q000473:pathology / Q000517:prevention & control; D010766:Phosphorylation / Q000502:physiology; D054388:Receptors, CCR / Q000096:biosynthesis*; D048051:p38 Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism*
C111835:CCL2 protein, human; C487531:CCRL2 protein, human; D018932:Chemokine CCL2; D054388:Receptors, CCR; D048051:p38 Mitogen-Activated Protein Kinases
Breast cancer; CCL2; CCRL2; Chemotaxis; Invasion; p38 MAPK