Evidence map›Paper›PMID 22142194›Full record

ArticleThe Biochemical journal2012

Secreted CXCL12 (SDF-1) forms dimers under physiological conditions.

Paramita Ray, Sarah A Lewin, Laura Anne Mihalko, Sasha-Cai Lesher-Perez, Shuichi Takayama, Kathryn E Luker, Gary D Luker

Abstract read
In one paragraph

Article in The Biochemical journal, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 35 papers.

0numbers the graph read from it
0cells of the map it votes in
35citing papers in PubMed
2.7field-weighted citation impact, top 9% 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

35 citing papers in PubMed, 59 citations in OpenAlex.

  1. Review
  2. Structural insights into CXCR4 modulation and oligomerization.Nature structural & molecular biology · 2025
    Article
  3. Review
  4. Article
  5. Review
  6. Article
  7. Review
  8. Article
  9. Review
  10. Article
  11. Review
  12. Review
  13. Article
  14. Article
  15. Review
  16. Review
  17. Article
  18. The unique structural and functional features of CXCL12.Cellular & molecular immunology · 2018
    Review
  19. CXCR7 Targeting and Its Major Disease Relevance.Frontiers in pharmacology · 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 1 institution in 1 country.

Paramita RayCenter for Molecular Imaging, Department of Radiology, University of Michigan, Ann Arbor, MI 48109, U.S.A.
Sarah A Lewin
Laura Anne Mihalko
Sasha-Cai Lesher-Perez
Shuichi Takayama
Kathryn E Luker
Gary D Luker
University of Michigan · US

Funding

Small Animal Imaging CoreP50CA093990 · NCI · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI ROSS, BRIAN D. · 2002 to 2012
$19.0M
Cellular Biotechnology Training Program (CBTP)T32GM008353 · NIGMS · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI SCHWENDEMAN, ANNA · 1991 to 2021
$9.3M
Cellular Biotechnology Training Program (CBTP) - Years 31-35T32GM145304 · NIGMS · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI Guizhi Zhu · 2022 to 2026
$2.6M
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 R01CA136829NIGMS NIH HHS T32 GM008353NIGMS NIH HHS T32 GM145304
6 · The paper itself

Abstract

Chemokine CXCL12 (CXC chemokine ligand 12) signalling through CXCR (CXC chemokine receptor) 4 and CXCR7 has essential functions in development and underlies diseases including cancer, atherosclerosis and autoimmunity. Chemokines may form homodimers that regulate receptor binding and signalling, but previous studies with synthetic CXCL12 have produced conflicting evidence for homodimerization. We used bioluminescence imaging with GL (Gaussia luciferase) fusions to investigate dimerization of CXCL12 secreted from mammalian cells. Using column chromatography and GL complementation, we established that CXCL12 was secreted from mammalian cells as both monomers and dimers. Secreted CXCL12 also formed homodimers in the extracellular space. Monomeric CXCL12 preferentially activated CXCR4 signalling through Gαi and Akt, whereas dimeric CXCL12 more effectively promoted recruitment of β-arrestin 2 to CXCR4 and chemotaxis of CXCR4-expressing breast cancer cells. We also showed that CXCR7 preferentially sequestered monomeric CXCL12 from the extracellular space and had minimal effects on dimeric CXCL12 in cell-based assays and an orthotopic tumour xenograft model of human breast cancer. These studies establish that CXCL12 secreted from mammalian cells forms homodimers under physiological conditions. Since monomeric and dimeric CXCL12 have distinct effects on cell signalling and function, our results have important implications for ongoing efforts to target CXCL12 pathways for therapy.

Indexed as

AnimalsBreast NeoplasmsCell Line, TumorChemokine CXCL12DimerizationExtracellular SpaceFemaleHEK293 CellsHumansLuciferases, FireflyMiceMice, Inbred NODMice, SCIDNeoplasm TransplantationProtein Structure, QuaternaryReceptors, CXCRACKR3 protein, humanChemokine CXCL12CXCL12 protein, humanCXCR4 protein, humanLuciferases, FireflyReceptors, CXCRReceptors, CXCR4Recombinant Fusion Proteins

Identifiers

PMID22142194
PMCPMC4419379
OpenAlexW2063394465

What OpenQuestion holds

Textmetadata
LicenceTDM
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.