Autocrine MCP-1/CCR2 signaling stimulates proliferation and migration of renal carcinoma cells

  • Authors:
    • Christoph Küper
    • Franz‑Xaver Beck
    • Wolfgang Neuhofer
  • View Affiliations

  • Published online on: July 18, 2016     https://doi.org/10.3892/ol.2016.4875
  • Pages: 2201-2209
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Abstract

The chemokine monocyte chemoattractant protein-1 [MCP-1; also known as chemokine (C-C motif) ligand 2] is an important mediator of monocyte recruitment during inflammatory processes. Pathologically high expression levels of MCP‑1 by tumor cells have been observed in a variety of cancer types. In the majority of cases, high MCP‑1 expression is associated with a poor prognosis, as infiltration of the tumor with inflammatory monocytes promotes tumor progression and metastasis. MCP‑1 is also expressed in renal cell carcinoma (RCC). In the present study, the function and the regulation of MCP‑1 was investigated in two RCC cell lines, CaKi‑1 and 786‑O. In both cell lines, expression of MCP‑1 was significantly enhanced compared with non‑cancerous control cells. As expected, secretion of MCP‑1 into the medium facilitated the recruitment of peripheral blood monocytes via the chemokine (C‑C motif) receptor type 2 (CCR2). As expression of CCR2 was also detected in 786‑O and CaKi‑1 cells, the effect of autocrine MCP‑1/CCR2 signaling was evaluated in these cells. In proliferation assays, administration of an MCP‑1 neutralizing antibody or of a CCR2 antagonist to CaKi‑1 and 786‑O cells significantly decreased cell growth; supplementation of the growth medium with recombinant human MCP‑1 had no additional effect on proliferation. The migration ability of RCC cells was impaired by MCP-1 neutralization or pharmacological CCR2 inhibition, while it was stimulated by the addition of recombinant human MCP-1, compared with untreated control cells. Finally, substantial differences in the regulation of MCP‑1 expression were observed between RCC cell lines. In CaKi‑1 cells, expression of MCP‑1 appears to be largely mediated by the transcription factor nuclear factor of activated T cells 5, while in 786‑O cells, deletion of the tumor suppressor gene Von-Hippel-Lindau appeared to be responsible for MCP‑1 upregulation, as suggested by previous studies. Taken together, the results of the current study indicate that expression of MCP‑1 in RCC cells promotes tumor progression and metastasis not only by paracrine, but also by autocrine, MCP‑1/CCR2 signaling events, enhancing cell proliferation and migration ability. Therefore, the present findings suggest the MCP-1/CCR2 axis is a potential target for future therapeutic strategies in the treatment of metastatic RCC.
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September-2016
Volume 12 Issue 3

Print ISSN: 1792-1074
Online ISSN:1792-1082

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Spandidos Publications style
Küper C, Beck FX and Neuhofer W: Autocrine MCP-1/CCR2 signaling stimulates proliferation and migration of renal carcinoma cells. Oncol Lett 12: 2201-2209, 2016
APA
Küper, C., Beck, F., & Neuhofer, W. (2016). Autocrine MCP-1/CCR2 signaling stimulates proliferation and migration of renal carcinoma cells. Oncology Letters, 12, 2201-2209. https://doi.org/10.3892/ol.2016.4875
MLA
Küper, C., Beck, F., Neuhofer, W."Autocrine MCP-1/CCR2 signaling stimulates proliferation and migration of renal carcinoma cells". Oncology Letters 12.3 (2016): 2201-2209.
Chicago
Küper, C., Beck, F., Neuhofer, W."Autocrine MCP-1/CCR2 signaling stimulates proliferation and migration of renal carcinoma cells". Oncology Letters 12, no. 3 (2016): 2201-2209. https://doi.org/10.3892/ol.2016.4875