PMID- 27602164
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20200929
IS  - 1792-1074 (Print)
IS  - 1792-1082 (Electronic)
IS  - 1792-1074 (Linking)
VI  - 12
IP  - 3
DP  - 2016 Sep
TI  - Autocrine MCP-1/CCR2 signaling stimulates proliferation and migration of renal 
      carcinoma cells.
PG  - 2201-2209
AB  - 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.
FAU - Kuper, Christoph
AU  - Kuper C
AD  - Department of Physiology, University of Munich, D-80336 Munich, Germany.
FAU - Beck, Franz-Xaver
AU  - Beck FX
AD  - Department of Physiology, University of Munich, D-80336 Munich, Germany.
FAU - Neuhofer, Wolfgang
AU  - Neuhofer W
AD  - Division of Nephrology and Rheumatology, Clinical Center Traunstein, D-83278 
      Traunstein, Germany.
LA  - eng
PT  - Journal Article
DEP - 20160718
PL  - Greece
TA  - Oncol Lett
JT  - Oncology letters
JID - 101531236
PMC - PMC4998526
OTO - NOTNLM
OT  - 786-O cells
OT  - CaKi-1 cells
OT  - autocrine signaling
OT  - chemokine (C-C motif) receptor type 2
OT  - monocyte chemoattractant protein-1
OT  - nuclear factor of activated T cells 5
OT  - renal cell carcinoma
EDAT- 2016/09/08 06:00
MHDA- 2016/09/08 06:01
PMCR- 2016/07/18
CRDT- 2016/09/08 06:00
PHST- 2015/07/30 00:00 [received]
PHST- 2016/05/13 00:00 [accepted]
PHST- 2016/09/08 06:00 [entrez]
PHST- 2016/09/08 06:00 [pubmed]
PHST- 2016/09/08 06:01 [medline]
PHST- 2016/07/18 00:00 [pmc-release]
AID - OL-0-0-4875 [pii]
AID - 10.3892/ol.2016.4875 [doi]
PST - ppublish
SO  - Oncol Lett. 2016 Sep;12(3):2201-2209. doi: 10.3892/ol.2016.4875. Epub 2016 Jul 
      18.