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Peer-reviewedCC BY 4.0JCI Insight

PTHrP induces breast cancer bone metastases via microbial-dependent expansion of TNF/IL-17–producing T cells

  • Nand K. Roy1,2
  • Subhashis Pal1,2
  • Hamid Y. Dar1,2
  • Sanchiti Patil1,2
  • M. Neale Weitzmann1,2,3
  • Roberto Pacifici1,2,4
4 affiliations
  1. 1Division of Endocrinology, Metabolism and Lipids, Department of Medicine, and
  2. 2Emory Microbiome Research Center, Emory University, Atlanta, Georgia.
  3. 3Joseph Maxwell Cleland Atlanta VA Healthcare System, Decatur, Georgia.
  4. 4Immunology and Molecular Pathogenesis Program, Emory University, Atlanta, Georgia, USA.
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Abstract

Bone metastases are a frequent complication of breast cancer, leading to reduced quality of life and increased morbidity. By intratibially injecting PyMT breast cancer cells in mice, we showed that the presence in the gut microbiome of segmented filamentous bacteria (SFB), a taxon that induces IL-17–producing Th17 cells and TNF-α (TNF)–producing T cells (TNF+ T cells), accelerated intraosseous tumor growth. SFB increased the activity of parathyroid hormone–related protein (PTHrP), a known driver of breast cancer bone metastasis produced by breast cancer cells. SFB promoted the PTHrP-induced expansion of intestinal Th17 cells and TNF+ T cells, their migration to bone marrow (BM) in tumor-bearing bones, and the BM expression of TNF, IL-17, and RANKL, cytokines that promote bone resorption. Demonstrating the functional relevance of IL-17 and TNF, silencing of either IL-17 or TNF blunted the growth of bone lesions in SFB+ mice. Thus, the abundance of SFB in the microbiome of mice and of SFB-like taxa in humans may determine the potency of PTHrP and the rate of growth of bone metastasis in breast cancer. Targeting the gut microbiota may represent a novel therapeutic strategy for breast cancer bone metastasis.

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Cite

BibTeXRIS
BibTeX
@article{roy2026pthrp,
  title = {{PTHrP induces breast cancer bone metastases via microbial-dependent expansion of TNF/IL-17–producing T cells}},
  author = {Nand K. Roy and Subhashis Pal and Hamid Y. Dar and Sanchiti Patil and M. Neale Weitzmann and Roberto Pacifici},
  journal = {JCI Insight},
  year = {2026},
  month = oct,
  doi = {10.1172/jci.insight.207567},
  url = {https://doi.org/10.1172/jci.insight.207567},
  note = {CC BY 4.0},
}
RIS
TY  - JOUR
TI  - PTHrP induces breast cancer bone metastases via microbial-dependent expansion of TNF/IL-17–producing T cells
AU  - Nand K. Roy
AU  - Subhashis Pal
AU  - Hamid Y. Dar
AU  - Sanchiti Patil
AU  - M. Neale Weitzmann
AU  - Roberto Pacifici
PY  - 2026
DA  - 2026/10/22
JO  - JCI Insight
DO  - 10.1172/jci.insight.207567
UR  - https://doi.org/10.1172/jci.insight.207567
AB  - Bone metastases are a frequent complication of breast cancer, leading to reduced quality of life and increased morbidity. By intratibially injecting PyMT breast cancer cells in mice, we showed that the presence in the gut microbiome of segmented filamentous bacteria (SFB), a taxon that induces IL-17–producing Th17 cells and TNF-α (TNF)–producing T cells (TNF+ T cells), accelerated intraosseous tumor growth. SFB increased the activity of parathyroid hormone–related protein (PTHrP), a known driver of breast cancer bone metastasis produced by breast cancer cells. SFB promoted the PTHrP-induced expansion of intestinal Th17 cells and TNF+ T cells, their migration to bone marrow (BM) in tumor-bearing bones, and the BM expression of TNF, IL-17, and RANKL, cytokines that promote bone resorption. Demonstrating the functional relevance of IL-17 and TNF, silencing of either IL-17 or TNF blunted the growth of bone lesions in SFB+ mice. Thus, the abundance of SFB in the microbiome of mice and of SFB-like taxa in humans may determine the potency of PTHrP and the rate of growth of bone metastasis in breast cancer. Targeting the gut microbiota may represent a novel therapeutic strategy for breast cancer bone metastasis.
SN  - 2379-3708
ER  -