Evidence map›Paper›PMID 24909174›Full record

ArticleOncogene2015

CXCL12-γ in primary tumors drives breast cancer metastasis.

P Ray, A C Stacer, J Fenner, S P Cavnar, K Meguiar, M Brown, K E Luker, G D Luker

Open access · bronzeAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Oncogene, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 38 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
38citing papers in PubMed, 1 pooled it
1.9field-weighted citation impact, top 13% 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

38 citing papers in PubMed, 1 synthesis or guideline pooled it, 59 citations in OpenAlex.

  1. Pooled it
  2. Review
  3. Review
  4. Article
  5. Article
  6. Article
  7. CXCL12-CXCR4/CXCR7 Axis in Cancer: from Mechanisms to Clinical Applications.International journal of biological sciences · 2023
    Review
  8. Article
  9. Article
  10. Article
  11. Article
  12. Review
  13. Article
  14. Review
  15. Article
  16. Article
  17. Article
  18. CXCL12 Signaling in the Tumor Microenvironment.Advances in experimental medicine and biology · 2021
    Review
  19. Article
  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

8 authors at 2 institutions in 1 country.

P RayCenter for Molecular Imaging, Department of Radiology, University of Michigan, Ann Arbor, MI, USA.
A C StacerCenter for Molecular Imaging, Department of Radiology, University of Michigan, Ann Arbor, MI, USA.
J FennerCenter for Molecular Imaging, Department of Radiology, University of Michigan, Ann Arbor, MI, USA.
S P CavnarDepartment of Biomedical Engineering, University of Michigan, Ann Arbor, MI, USA.
K MeguiarCenter for Molecular Imaging, Department of Radiology, University of Michigan, Ann Arbor, MI, USA.
M BrownBreast Oncology Program, Comprehensive Cancer Center, Department of Internal Medicine, University of Michigan, Ann Arbor, MI, USA.
K E LukerCenter for Molecular Imaging, Department of Radiology, University of Michigan, Ann Arbor, MI, USA.
G D Luker1] Center for Molecular Imaging, Department of Radiology, University of Michigan, Ann Arbor, MI, USA [2] Department of Biomedical Engineering, University of Michigan, Ann Arbor, MI, USA [3] Breast Oncology Program, Comprehensive Cancer Center, Department of Internal Medicine, University of Michigan, Ann Arbor, MI, USA [4] Department of Microbiology and Immunology, University of Michigan Center, Ann Arbor, MI, USA
University of Michigan–Ann Arbor · USMichigan Medicine · US

Funding

Small Animal Imaging CoreP50CA093990 · NCI · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI ROSS, BRIAN D. · 2002 to 2012
$19.0M
Targeted Multi-Spectral Dual Axes Confocal Imaging of In Vivo Molecular ExpressioR01CA142750 · NCI · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI KURABAYASHI, KATSUO, LUKER, GARY D · 2010 to 2014
$2.4M
Microfluidic Models of Metastatic CancerR01CA136829 · NCI · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI LUKER, GARY D · 2009 to 2013
$1.5M
Molecular Imaging of Chemokine Receptor SignalingR01CA136553 · NCI · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI LUKER, GARY D · 2009 to 2013
$1.5M
NCI NIH HHS P50 CA093990NCI NIH HHS P50CA093990NCI NIH HHS R01 CA136553NCI NIH HHS R01CA136553NCI NIH HHS R01 CA136829NCI NIH HHS R01CA136829NCI NIH HHS R01 CA142750NCI NIH HHS R01CA142750
6 · The paper itself

Abstract

Compelling evidence shows that chemokine C-X-C motif chemokine ligand 12 (CXCL12) drives metastasis in multiple malignancies. Similar to other key cytokines in cancer, CXCL12 exists as several isoforms with distinct biophysical properties that may alter signaling and functional outputs. However, effects of CXCL12 isoforms in cancer remain unknown. CXCL12-α, -β and -γ showed cell-type-specific differences in activating signaling through G protein-dependent pathways in cell-based assays, while CXCL12-γ had greatest effects on recruitment of the adapter protein β-arrestin 2. CXCL12-β and -γ also stimulated endothelial tube formation to a greater extent than CXCL12-α. To investigate the effects of CXCL12 isoforms on tumor growth and metastasis, we used a mouse xenograft model of metastatic human breast cancer combining CXCR4+ breast cancer cells and mammary fibroblasts secreting an isoform of CXCL12. Altough all CXCL12 isoforms produced comparable growth of mammary tumors, CXCL12-γ significantly increased metastasis to bone marrow and other sites. Breast cancer cells originating from tumors with CXCL12-γ fibroblasts upregulated RANKL (receptor activator of nuclear factor-κB ligand), contributing to bone marrow tropism of metastatic cancer cells. CXCL12-γ was expressed in metastatic tissues in mice, and we also detected CXCL12-γ in malignant pleural effusions from patients with breast cancer. In our mouse model, mammary fibroblasts disseminated to sites of breast cancer metastases, providing another mechanism to increase levels of CXCL12 in metastatic environments. These studies identify CXCL12-γ as a potent pro-metastatic molecule with important implications for cancer biology and effective therapeutic targeting of CXCL12 pathways.

Indexed as

AnimalsArrestinsbeta-Arrestin 2beta-ArrestinsBone NeoplasmsBreast NeoplasmsCells, CulturedChemokine CXCL12FemaleGene Expression Regulation, NeoplasticHumansHuman Umbilical Vein Endothelial CellsMiceProtein IsoformsRANK LigandReceptors, CXCR4ARRB2 protein, humanArrb2 protein, mouseArrestinsbeta-Arrestin 2beta-ArrestinsChemokine CXCL12CXCL12 protein, humanCXCR4 protein, humanProtein IsoformsRANK LigandReceptors, CXCR4TNFSF11 protein, human

Identifiers

PMID24909174
PMCPMC4261050
OpenAlexW2018299899

What OpenQuestion holds

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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.