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The contribution of stem cell factor and its receptor c-Kit to cancer-induced bone pain.

Overview

Authors: Kelly F Contino1, Jenna Ollodart1, Yang Yu1, Sun H Park1,2, Shunsuke Tsuzuki1,3, Kara Rollins1, Tyler M Heethouse1, Joshua Chu1, Laiton R Steele1,4, Takahiro Kimura3, Jingyun Lee5, Cristina M Furdui5, Lance D Miller1, Fang-Chi Hsu6, Yusuke Shiozawa1
ORCID iDs: Kelly F Contino, Jenna Ollodart, Shunsuke Tsuzuki, Laiton R Steele, Takahiro Kimura, Cristina M Furdui, Yusuke Shiozawa
  1. Department of Cancer Biology and Atrium Health Wake Forest Baptist Comprehensive Cancer Center and
  2. Department of Radiation Oncology, Wake Forest University School of Medicine, Winston-Salem, North Carolina, USA
  3. Department of Urology, The Jikei University School of Medicine, Tokyo, Japan
  4. Department of PA Studies
  5. Department of Internal Medicine, Section on Molecular Medicine, and
  6. Department of Biostatistics and Data Science, Wake Forest University School of Medicine, Winston-Salem, North Carolina, USA
Institutions: Wake Forest Baptist Comprehensive Cancer Center; Wake Forest University Health Sciences (United States); Wake Forest University (United States); Jikei University School of Medicine (Japan)
Journal: JCI insight, volume 11, issue 12, article e191905
Dates: received 3 February 2025; accepted 30 April 2026; published online 5 May 2026
Type: Research article · Language: English
License: CC BY
Identifiers: DOI 10.1172/jci.insight.191905 · PMID 42084950 · PMCID PMC13313531 · OpenAlex W7160280310
Open access: gold, a free copy (OpenAlex)
Status: data only
Categories: human (organism), mouse (organism), other condition (population), pain (population), cellular / molecular (subfield)
Methods: Preprocessing, Statistics, Smoothing, state filtering, decompositions, Machine learning, Evoked potentials
Keywords: Neuroscience, Oncology, Pain
MeSH: Bone Neoplasms*, Cancer Pain*, Proto-Oncogene Proteins c-kit*, Stem Cell Factor*, Animals, Cell Line, Tumor, Female, Ganglia, Spinal, Humans, Mice, Sensory Receptor Cells, Signal Transduction (* major topic)
Topic: Mast cells and histamine (Immunology, Immunology and Microbiology), according to OpenAlex
Funding: U.S. Department of Defense (W81XWH-17-1-0541,W81XWH-19-1-0045); National Cancer Institute (R01CA238888,R21CA297068,P30CA012197); NCI NIH HHS (R21 CA297068, R01 CA238888); METAvivor (METAvivor Research Award)
Citations: not cited yet (Europe PMC); 85 references in the paper

Abstract

Cancer-induced bone pain (CIBP) is among the most common and debilitating symptoms in patients with bone metastasis. Current treatments are somewhat effective but have severe side effects. For the future development of safer CIBP treatments, in this study, we sought to investigate the mechanisms whereby the nerve-cancer interaction controls CIBP. We found that c-Kit, a receptor tyrosine kinase, was activated in the dorsal root ganglia (DRG) sensory neurons of mice with CIBP and that c-Kit’s sole ligand, stem cell factor (SCF), was enhanced in the bone marrow with bone metastasis. When DRGs were treated with SCF or conditioned medium from high SCF-expressing cancer cells, in vitro nerve sprouting was enhanced, and this effect was abolished with c-Kit inhibitors. Mice inoculated intrafemorally with cancer cells that had varying levels of SCF expression developed CIBP and enhanced peripheral nerve sprouting in an SCF-dependent manner. Downstream proteomic analysis revealed that SCF upregulated and activated fibroblast growth factor 1 (FGF1) in DRGs. When FGF1 was knocked down in DRGs, SCF-mediated nerve sprouting was prevented. Taken together, our studies demonstrate the importance of the SCF/c-Kit axis in CIBP and nerve sprouting and identify the SCF/c-Kit/FGF1 pathway as a potential therapeutic target for CIBP.

Reproduced under the paper's license (CC BY), from the paper cited above.

Code

The paper links to its data, not to its authors' code: see the Data section.

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Data

Datasets cited

Data availability

All data that support this study’s findings are available in the main text or supplemental materials. The corresponding values for all data points in graphs are reported in the Supporting Data Values file. Single-cell sequencing results have been deposited into Gene Expression Omnibus (GSE325147 (https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE325147)). The mass spectrometry proteomics data have been deposited to the ProteomeXchange Consortium via the PRIDE (85) partner repository with the dataset identifier PXD076785 and 10.6019/PXD076785. For other original data or detailed protocols, contact the corresponding author.

Reproduced under the paper's license (CC BY), from the paper cited above.

Versions

The history of this record: each version stored by the harvester or made by a correction of its authors or of the maintainers of its code, and what changed in its facts. The texts of the paper (its abstract, its availability statements) are not part of it; versions that changed only those are not listed.

Version 2, 28 September 2026

  • Authors: added Jenna Ollodart (0000-0003-4837-4194); Shunsuke Tsuzuki (0000-0001-6164-4684); Cristina M Furdui (0000-0003-3771-7999); Yusuke Shiozawa (0000-0001-9814-9230); removed Jenna Ollodart; Shunsuke Tsuzuki; Cristina M Furdui; Yusuke Shiozawa

Version 1, 28 September 2026: the first record

Recorded: type, language, journal, volume, issue, pages, dates, 15 authors, 3 keywords, 12 MeSH terms, 4 funders, 85 references.

Cite

This paper

Contino, K. F., Ollodart, J., Yu, Y., Park, S. H., Tsuzuki, S., Rollins, K., Heethouse, T. M., Chu, J., Steele, L. R., Kimura, T., Lee, J., Furdui, C. M., Miller, L. D., Hsu, F.-C., & Shiozawa, Y. (2026). The contribution of stem cell factor and its receptor c-Kit to cancer-induced bone pain. JCI insight, 11(12), e191905. https://doi.org/10.1172/jci.insight.191905

BibTeX

@article{contino2026contribution,
author = {Contino, Kelly F and Ollodart, Jenna and Yu, Yang and Park, Sun H and Tsuzuki, Shunsuke and Rollins, Kara and Heethouse, Tyler M and Chu, Joshua and Steele, Laiton R and Kimura, Takahiro and Lee, Jingyun and Furdui, Cristina M and Miller, Lance D and Hsu, Fang-Chi and Shiozawa, Yusuke},
title = {{The contribution of stem cell factor and its receptor c-Kit to cancer-induced bone pain}},
journal = {JCI insight},
year = {2026},
month = may,
volume = {11},
number = {12},
pages = {e191905},
publisher = {American Society for Clinical Investigation},
issn = {2379-3708},
doi = {10.1172/jci.insight.191905},
url = {https://doi.org/10.1172/jci.insight.191905},
pmid = {42084950},
pmcid = {PMC13313531}
}

RIS

TY - JOUR
AU - Contino, Kelly F
AU - Ollodart, Jenna
AU - Yu, Yang
AU - Park, Sun H
AU - Tsuzuki, Shunsuke
AU - Rollins, Kara
AU - Heethouse, Tyler M
AU - Chu, Joshua
AU - Steele, Laiton R
AU - Kimura, Takahiro
AU - Lee, Jingyun
AU - Furdui, Cristina M
AU - Miller, Lance D
AU - Hsu, Fang-Chi
AU - Shiozawa, Yusuke
TI - The contribution of stem cell factor and its receptor c-Kit to cancer-induced bone pain
T2 - JCI insight
J2 - JCI Insight
PY - 2026
DA - 2026/05/05
VL - 11
IS - 12
SP - e191905
SN - 2379-3708
PB - American Society for Clinical Investigation
DO - 10.1172/jci.insight.191905
UR - https://doi.org/10.1172/jci.insight.191905
LA - en
ER -

CSL-JSON

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