Evidence map›Paper›PMID 20651241›Full record

ArticleThe American journal of pathology2010

Notch3 in human breast cancer cell lines regulates osteoblast-cancer cell interactions and osteolytic bone metastasis.

Zhiyuan Zhang, Hao Wang, Sadakatsu Ikeda, Frederic Fahey, Diane Bielenberg, Patrick Smits, Peter V Hauschka

Open access · bronzeAbstract read
In one paragraph

Article in The American journal of pathology, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 37 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
37citing 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

37 citing papers in PubMed, 1 synthesis or guideline pooled it, 65 citations in OpenAlex.

  1. Pooled it
  2. Trial
  3. Review
  4. Review
  5. Article
  6. Review
  7. Article
  8. Roles of Notch Signaling in the Tumor Microenvironment.International journal of molecular sciences · 2022
    Review
  9. Mammary Development and Breast Cancer: a Notch Perspective.Journal of mammary gland biology and neoplasia · 2021
    Review
  10. Review
  11. Notch Signalling in Breast Development and Cancer.Frontiers in cell and developmental biology · 2021
    Review
  12. Review
  13. Review
  14. Article
  15. Review
  16. Article
  17. Article
  18. Review
  19. Notch in skeletal physiology and disease.Osteoporosis international : a journal established as result of cooperation between the European Foundation for Osteoporosis and the National Osteoporosis Foundation of the USA · 2018
    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

7 authors at 3 institutions in 2 countries.

Zhiyuan ZhangDepartment Orthopaedic Surgery, Children's Hospital Boston, Boston, MA 02115, USA.
Hao Wang
Sadakatsu Ikeda
Frederic Fahey
Diane Bielenberg
Patrick Smits
Peter V Hauschka
Boston Children's Hospital · USBoston Children's Museum · USHarvard University · US

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Breast cancer preferentially metastasizes to bone. We therefore addressed the role of Notch signaling in osteoblast-cancer cell interactions and in bone metastasis. Human bone marrow osteoblasts selectively enhanced the expression of Notch3 and its ligand Jagged1 in human breast cancer cell lines. Osteoblasts also stimulated cancer cell colony formation in soft agar, which was reduced by a chemical inhibitor of Notch signaling and anti-transforming growth factor beta1 (TGFbeta1) antibody. TGFbeta1, a major prometastatic product of osteoblasts, also stimulated cancer cell Notch3 expression. Notch3 knockdown in the cancer cells by stable short hairpin RNA interference decreased the osteoblast- and TGFbeta1-stimulated colony formation as well as TGFbeta1-mediated Smad3/Smad2 phosphorylation; Jagged1 level was coordinately reduced. In addition, expression of snail, a regulator of epithelial-mesenchymal transition, and the mesenchymal markers fibronectin and vimentin was attenuated by reducing Notch3 levels. To study the role of Notch3 signaling in bone metastasis, cancer cells were inoculated into athymic mice, either into femoral bone marrow cavities or into the systemic circulation via the left ventricle. Compared with robust osteolysis in mice receiving control cells, osteolytic lesions were significantly reduced following inoculation of cells with constitutively reduced Notch3 expression. Taken together, our results suggest that enhanced Notch3 expression in breast cancer cells, triggered by osteoblasts and their secretion of TGFbeta1 in the bone marrow niche, may stand as a novel mechanism for promoting bone metastasis.

Indexed as

AnimalsApoptosisBone and BonesBone NeoplasmsBreast NeoplasmsCell Line, TumorCell ProliferationCoculture TechniquesEnzyme-Linked Immunosorbent AssayFemaleHumansMiceMice, NudeNeoplasm TransplantationOsteoblastsOsteolysisNOTCH3 protein, humanReceptor, Notch3Receptors, NotchTransforming Growth Factor beta1

Identifiers

PMID20651241
PMCPMC2928977
OpenAlexW2031445014

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.