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Updated: Sep 24, 2025
Dual Effects of Melanoma Cell-derived Factors on Bone Marrow Adipocytes Differentiation
Published on: August 23, 2018
The microbiome restrains melanoma bone growth by promoting intestinal NK and Th1 cell homing to bone
Subhashis Pal1,2, Daniel S Perrien1,2, Tetsuya Yumoto3
1Division of Endocrinology, Metabolism and Lipids, Department of Medicine, and.
Abstract:
Bone metastases are frequent complications of malignant melanoma leading to reduced quality of life and significant morbidity. Regulation of immune cells by the gut microbiome influences cancer progression, but the role of the microbiome in tumor growth in bone is unknown. Using intracardiac or intratibial injections of B16-F10 melanoma cells into mice, we showed that gut microbiome depletion by broad-spectrum antibiotics accelerated intraosseous tumor growth and osteolysis. Microbiome depletion blunted melanoma-induced expansion of intestinal NK cells and Th1 cells and their migration from the gut to tumor-bearing bones. Demonstrating the functional relevance of immune cell trafficking from the gut to the bone marrow (BM) in bone metastasis, blockade of S1P-mediated intestinal egress of NK and Th1 cells, or inhibition of their CXCR3/CXCL9-mediated influx into the BM, prevented the expansion of BM NK and Th1 cells and accelerated tumor growth and osteolysis. Using a mouse model, this study revealed mechanisms of microbiota-mediated gut-bone crosstalk that are relevant to the immunological restraint of melanoma metastasis and tumor growth in bone. Microbiome modifications induced by antibiotics might have negative clinical consequences in patients with melanoma.
Insights
The gut microbiome restrains melanoma bone metastasis by promoting immune cell migration from the gut to bone. Depleting the microbiome accelerates tumor growth and bone destruction, highlighting potential negative impacts of antibiotics in melanoma patients.
Area of Science:
- Immunology
- Oncology
- Microbiology
Background:
- Bone metastases are common in malignant melanoma, impacting patient quality of life.
- The gut microbiome's role in regulating immune cells and cancer progression is known, but its specific influence on bone metastasis is unclear.
Purpose of the Study:
- To investigate the role of the gut microbiome in melanoma bone metastasis.
- To elucidate the mechanisms of microbiota-mediated gut-bone crosstalk in melanoma progression.
Main Methods:
- Utilized a mouse model with B16-F10 melanoma cells injected intracardiac or intratibial.
- Administered broad-spectrum antibiotics to deplete the gut microbiome.
- Blocked S1P-mediated immune cell egress from the intestine and CXCR3/CXCL9-mediated influx into bone marrow (BM).
Main Results:
- Gut microbiome depletion accelerated intraosseous tumor growth and osteolysis.
- Microbiome depletion reduced intestinal NK and Th1 cell expansion and their migration to bone.
- Blocking immune cell trafficking from gut to BM prevented immune cell expansion and exacerbated tumor growth and osteolysis.
Conclusions:
- The gut microbiome plays a crucial role in restraining melanoma metastasis to bone via immune cell modulation and trafficking.
- Antibiotic-induced microbiome alterations may negatively impact melanoma progression and treatment outcomes.
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