Evidence map›Paper›PMID 27666332›Full record

ArticleCancer medicine2016

CCL2 as a potential therapeutic target for clear cell renal cell carcinoma.

Ryuichiro Arakaki, Toshinari Yamasaki, Toru Kanno, Noboru Shibasaki, Hiromasa Sakamoto, Noriaki Utsunomiya, Takayuki Sumiyoshi, Shinsuke Shibuya, Tatsuaki Tsuruyama, Eijiro Nakamura and 2 more

Open access · goldAbstract read
In one paragraph

Article in Cancer medicine, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 48 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
48citing papers in PubMed, 1 pooled it
2.0field-weighted citation impact, top 14% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

48 citing papers in PubMed, 1 synthesis or guideline pooled it, 61 citations in OpenAlex.

  1. Pooled it
  2. Article
  3. JUNB and JUND in Urological Cancers: A Literature Review.Current issues in molecular biology · 2025
    Review
  4. Article
  5. Review
  6. Review
  7. Article
  8. Review
  9. Article
  10. Review
  11. Article
  12. Review
  13. JunB: a paradigm for Jun family in immune response and cancer.Frontiers in cellular and infection microbiology · 2023
    Review
  14. Review
  15. Article
  16. Article
  17. Review
  18. Review
  19. Review
  20. Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

12 authors at 1 institution in 1 country.

Ryuichiro ArakakiDepartment of Urology, Kyoto University Graduate School of Medicine, Kyoto, Japan.
Toshinari YamasakiDepartment of Urology, Kyoto University Graduate School of Medicine, Kyoto, Japan.
Toru KannoDepartment of Urology, Kyoto University Graduate School of Medicine, Kyoto, Japan.
Noboru ShibasakiDepartment of Urology, Kyoto University Graduate School of Medicine, Kyoto, Japan.
Hiromasa SakamotoDepartment of Urology, Kyoto University Graduate School of Medicine, Kyoto, Japan.
Noriaki UtsunomiyaDepartment of Urology, Kyoto University Graduate School of Medicine, Kyoto, Japan.
Takayuki SumiyoshiDepartment of Urology, Kyoto University Graduate School of Medicine, Kyoto, Japan.
Shinsuke ShibuyaDepartment of Diagnostic Pathology, Kyoto University Graduate School of Medicine, Kyoto, Japan.
Tatsuaki TsuruyamaDepartment of Diagnostic Pathology, Kyoto University Graduate School of Medicine, Kyoto, Japan.
Eijiro NakamuraLaboratory for Malignancy Control Research/Medical Innovation Center, Kyoto University Graduate School of Medicine, Kyoto, Japan.
Osamu OgawaDepartment of Urology, Kyoto University Graduate School of Medicine, Kyoto, Japan.
Tomomi KambaDepartment of Urology, Kyoto University Graduate School of Medicine, Kyoto, Japan. kamba@kuhp.kyoto-u.ac.jp.
Kyoto University · JP

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

We previously reported that the pVHL-atypical PKC-JunB pathway contributed to promotion of cell invasiveness and angiogenesis in clear cell renal cell carcinoma (ccRCC), and we detected chemokine (C-C motif) ligand-2 (CCL2) as one of downstream effectors of JunB. CCL2 plays a critical role in tumorigenesis in other types of cancer, but its role in ccRCC remains unclear. In this study, we investigated the roles and therapeutic potential of CCL2 in ccRCC. Immunohistochemical analysis of CCL2 expression for ccRCC specimens showed that upregulation of CCL2 expression correlated with clinical stage, overall survival, and macrophage infiltration. For functional analysis of CCL2 in ccRCC cells, we generated subclones of WT8 cells that overexpressed CCL2 and subclones 786-O cells in which CCL2 expression was knocked down. Although CCL2 expression did not affect cell proliferation in vitro, CCL2 overexpression enhanced and CCL2 knockdown suppressed tumor growth, angiogenesis, and macrophage infiltration in vivo. We then depleted macrophages from tumor xenografts by administration of clodronate liposomes to confirm the role of macrophages in ccRCC. Depletion of macrophages suppressed tumor growth and angiogenesis. To examine the effect of inhibiting CCL2 activity in ccRCC, we administered CCL2 neutralizing antibody to primary RCC xenografts established from patient surgical specimens. Inhibition of CCL2 activity resulted in significant suppression of tumor growth, angiogenesis, and macrophage infiltration. These results suggest that CCL2 is involved in angiogenesis and macrophage infiltration in ccRCC, and that CCL2 could be a potential therapeutic target for ccRCC.

Indexed as

Up-RegulationAdultAgedAged, 80 and overAnimalsCarcinoma, Renal CellCell Line, TumorCell ProliferationChemokine CCL2FemaleGene Expression Regulation, NeoplasticHumansKidney NeoplasmsMacrophagesMaleMiceCCL2 protein, humanChemokine CCL2Angiogenesischemokine (C-C motif) ligand-2renal cell carcinomatumor macrophagexenograft

Identifiers

PMID27666332
PMCPMC5083746
OpenAlexW2527362689

What OpenQuestion holds

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LicenceCC BY
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.