Evidence map›Paper›PMID 25223386›Full record

ArticleClinical & experimental metastasis2014

Targeting IL-6 and RANKL signaling inhibits prostate cancer growth in bone.

Yu Zheng, Dennis Basel, Shu-Oi Chow, Colette Fong-Yee, Sarah Kim, Frank Buttgereit, Colin R Dunstan, Hong Zhou, Markus J Seibel

Abstract read
PubMed Publisher
In one paragraph

Article in Clinical & experimental metastasis, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
27citing papers in PubMed, 1 pooled it
3.0field-weighted citation impact, top 8% 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

27 citing papers in PubMed, 1 synthesis or guideline pooled it, 44 citations in OpenAlex.

  1. Pooled it
  2. Review
  3. Article
  4. Review
  5. Review
  6. Article
  7. Article
  8. Article
  9. Review
  10. Article
  11. Review
  12. Review
  13. Review
  14. Review
  15. Review
  16. Hallmarks of Bone Metastasis.Calcified tissue international · 2018
    Review
  17. Review
  18. Review
  19. Review
  20. Article
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

9 authors at 3 institutions in 2 countries.

Yu ZhengBone Research Program, ANZAC Research Institute, University of Sydney, Sydney, NSW, 2139, Australia, yu.zheng@sydney.edu.au.
Dennis Basel
Shu-Oi Chow
Colette Fong-Yee
Sarah Kim
Frank Buttgereit
Colin R Dunstan
Hong Zhou
Markus J Seibel
Anzac Research Institute · AUUniversity of Sydney · AUBerlin-Brandenburger Centrum für Regenerative Therapien · DE

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

In prostate cancer metastases to bone, cancer cell-derived cytokines stimulate RANKL expression by cells of the osteoblast lineage, which in turn activates osteoclastic bone resorption. However, it is unclear whether cells of the osteoblast lineage signal back to prostate cancer cells, and if so, whether such direct cross-talk can be targeted therapeutically. Using the human prostate cancer cell line, PC3, we identified two novel signalling pathways acting between cells of the osteoblast lineage and cancer cells. First, exposure to RANKL stimulated the expression and release of IL-6 by PC3 cells in vitro (which is known to promote RANKL expression by osteoblasts). Second, treatment of PC3 cells with IL-6 increased the expression of RANK, the cognate receptor of RANKL, and enhanced the RANKL-induced release of IL-6 by PC3 cells. Third, targeted disruption of IL-6 signaling with tocilizumab, a clinically available antibody against the human IL-6 receptor, inhibited skeletal tumor growth in vivo and reduced serum RANKL levels as well as RANK expression by PC3-derived bone tumors. Similar effects were achieved when RANK expression was knocked down in PC3 cells. In contrast, disruption of IL-6 or RANK/RANKL signalling had no effect on PC3 tumor growth in soft tissues, indicating that these signalling pathways act specifically within the bone microenvironment. In conclusion, prostate cancer cells and cells of the osteoblast lineage communicate via two inter-dependent signaling pathways, which through auto-amplification strongly enhance metastatic prostate cancer growth in bone. Both pathways may be targeted for effective therapeutic intervention.

Indexed as

Interleukin-6 InhibitorsAnimalsAntibodies, Monoclonal, HumanizedBlotting, WesternBone NeoplasmsCoculture TechniquesHumansImmunoenzyme TechniquesInterleukin-6MaleMiceOsteoblastsProstatic NeoplasmsRANK LigandReal-Time Polymerase Chain ReactionReceptors, Interleukin-6Antibodies, Monoclonal, HumanizedInterleukin-6Interleukin-6 InhibitorsRANK LigandReceptors, Interleukin-6RNA, Messengertocilizumab

Identifiers

PMID25223386
OpenAlexW1981386560

What OpenQuestion holds

Textmetadata
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.