Evidence map›Paper›PMID 42669113›Full record

ReviewClinical & experimental metastasis2026

CX3CL1/CX3CR1 signaling in spinal metastasis: mechanisms and translational opportunities.

Vivek Sanker, Zhikai Li, Adrian Urdaneta, Aaditya Dravid, Philip Heesen, Joseph Frantzias, Maria Jose Cavagnaro, John Ratliff, Irimpan Mathews, Atman Desai

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In one paragraph

Review in Clinical & experimental metastasis, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

0numbers the graph read from it
0cells of the map it votes in
0citing papers in PubMed
–field-weighted citation impact
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

0 citing papers in PubMed.

No citing paper in PubMed yet.

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

10 authors.

Vivek Sanker *Department of Neurosurgery, Stanford University, Stanford, CA, USA. vsanker@stanford.edu.
Zhikai Li *Department of Clinical Neurosciences, Addenbrooke's Hospital, Cambridge, UK.
Adrian UrdanetaDepartment of Neurosurgery, Hospital Miguel Perez Carreño, Caracas, Venezuela.
Aaditya DravidDepartment of Neurosurgery, Imperial College London School of Medicine, London, UK.
Philip HeesenFaculty of Medicine, University of Zurich, Zurich, Switzerland.
Joseph FrantziasDepartment of Neurosurgery, Stanford University, Stanford, CA, USA.
Maria Jose CavagnaroDepartment of Neurosurgery, Stanford University, Stanford, CA, USA.
John RatliffDepartment of Neurosurgery, Stanford University, Stanford, CA, USA.
Irimpan MathewsStanford Synchrotron Radiation Lightsource, Menlo Park, CA, USA.
Atman DesaiDepartment of Neurosurgery, Stanford University, Stanford, CA, USA.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundSpinal metastases are a common and morbid complication of advanced malignancies. While vertebral involvement is often attributed to anatomical factors, emerging evidence implicates the chemokine CX3CL1 and its receptor in guiding tumor cells to the spine and reshaping the bone microenvironment.

objectiveTo systematically review the role of the CX3CL1/CX3CR1 axis in spinal metastasis from primary breast, prostate, and liver tumours, synthesizing mechanistic, preclinical, and translational findings.

methodsFollowing PRISMA guidelines, we searched Medline, EMBASE, Web of Science, and Scopus from inception to May 27, 2025, identifying original studies on CX3CL1/CX3CR1 signalling in spinal metastasis. Ten studies met inclusion criteria. Data were extracted across study design, tumour model, expression analysis, mechanisms, and therapeutic or prognostic outcomes. We also analysed experimentally determined CX3CL1 and CX3CR1 structures to identify features relevant to inhibitor design.

resultsCX3CL1 expression was three-fold higher in spinal metastases than in primary tumours or non-spinal bone. Mechanistic studies showed roles in chemotaxis, Src/FAK and PI3K/AKT activation, EMT, vascular permeability, and immunomodulation. CX3CL1 also activated stromal pathways promoting osteolysis. Pharmacologic inhibition reduced spinal metastasis and restored chemosensitivity in murine models. Elevated serum CX3CL1/CX3CR1 levels correlated with disease burden in patient cohorts.

conclusionThe CX3CL1/CX3CR1 axis contributes to spinal metastasis by integrating tumour-intrinsic signalling with vertebral niche remodelling, extending the seed-and‑soil hypothesis. Its consistent activity and tractability highlight its promise as both biomarker and therapeutic target in metastatic spine disease.

Indexed as

Chemokine CX3CL1CX3C Chemokine Receptor 1Spinal NeoplasmsAnimalsHumansSignal TransductionTumor MicroenvironmentChemokine CX3CL1CX3C Chemokine Receptor 1CX3CL1 protein, humanCX3CR1 protein, humanChemokine signalingCX3CL1/CX3CR1 axisSpinal metastasisTranslational oncologyTumor microenvironment

Identifiers

PMID42669113

What OpenQuestion holds

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Registered trials

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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.