دورية أكاديمية
The microbiome restrains melanoma bone growth by promoting intestinal NK and Th1 cell homing to bone.
العنوان: | The microbiome restrains melanoma bone growth by promoting intestinal NK and Th1 cell homing to bone. |
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المؤلفون: | Pal S; Division of Endocrinology, Metabolism and Lipids, Department of Medicine, and.; Emory Microbiome Research Center, Emory University, Atlanta, Georgia, USA., Perrien DS; Division of Endocrinology, Metabolism and Lipids, Department of Medicine, and.; Emory Microbiome Research Center, Emory University, Atlanta, Georgia, USA., Yumoto T; Department of Surgery and Emory Critical Care Center, Emory University School of Medicine, Atlanta, Georgia, USA., Faccio R; Department of Orthopedics, Washington University in St. Louis, St. Louis, Missouri, USA., Stoica A; Division of Endocrinology, Metabolism and Lipids, Department of Medicine, and.; Emory Microbiome Research Center, Emory University, Atlanta, Georgia, USA., Adams J; Division of Endocrinology, Metabolism and Lipids, Department of Medicine, and.; Emory Microbiome Research Center, Emory University, Atlanta, Georgia, USA., Coopersmith CM; Emory Microbiome Research Center, Emory University, Atlanta, Georgia, USA.; Department of Surgery and Emory Critical Care Center, Emory University School of Medicine, Atlanta, Georgia, USA., Jones RM; Emory Microbiome Research Center, Emory University, Atlanta, Georgia, USA.; Division of Pediatric Gastroenterology, Hepatology, and Nutrition, Department of Pediatrics, Emory University, Atlanta, Georgia, USA., Weitzmann MN; Division of Endocrinology, Metabolism and Lipids, Department of Medicine, and.; Emory Microbiome Research Center, Emory University, Atlanta, Georgia, USA.; Atlanta VA Health Care System, Department of Veterans Affairs, Decatur, Georgia, USA., Pacifici R; Division of Endocrinology, Metabolism and Lipids, Department of Medicine, and.; Emory Microbiome Research Center, Emory University, Atlanta, Georgia, USA.; Immunology and Molecular Pathogenesis Program, Emory University, Atlanta, Georgia, USA. |
المصدر: | The Journal of clinical investigation [J Clin Invest] 2022 Jun 15; Vol. 132 (12). |
نوع المنشور: | Journal Article; Research Support, U.S. Gov't, Non-P.H.S.; Research Support, N.I.H., Extramural |
اللغة: | English |
بيانات الدورية: | Publisher: American Society for Clinical Investigation Country of Publication: United States NLM ID: 7802877 Publication Model: Print Cited Medium: Internet ISSN: 1558-8238 (Electronic) Linking ISSN: 00219738 NLM ISO Abbreviation: J Clin Invest Subsets: MEDLINE |
أسماء مطبوعة: | Publication: 1999- : Ann Arbor, MI : American Society for Clinical Investigation Original Publication: New Haven [etc.] American Society for Clinical Investigation. |
مواضيع طبية MeSH: | Gastrointestinal Microbiome* , Melanoma, Experimental*/pathology , Osteolysis*, Animals ; Anti-Bacterial Agents/pharmacology ; Bone Development ; Humans ; Mice ; Mice, Inbred C57BL ; Quality of Life ; Th1 Cells/pathology |
مستخلص: | 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. |
التعليقات: | Comment in: Nat Rev Cancer. 2022 Sep;22(9):494-495. (PMID: 35941222) |
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معلومات مُعتمدة: | R01 DK112946 United States DK NIDDK NIH HHS; S10 RR028009 United States RR NCRR NIH HHS; U54 AG062334 United States AG NIA NIH HHS; R01 CA270030 United States CA NCI NIH HHS; R01 GM072808 United States GM NIGMS NIH HHS; R01 AR066551 United States AR NIAMS NIH HHS; R01 GM104323 United States GM NIGMS NIH HHS; R01 DK119229 United States DK NIDDK NIH HHS; R01 DK124821 United States DK NIDDK NIH HHS; T32 GM095442 United States GM NIGMS NIH HHS; R01 AR079298 United States AR NIAMS NIH HHS; R01 AR068157 United States AR NIAMS NIH HHS; R01 AR070091 United States AR NIAMS NIH HHS; I01 BX000105 United States BX BLRD VA; R01 CA235096 United States CA NCI NIH HHS |
فهرسة مساهمة: | Keywords: Bone Biology; Melanoma |
المشرفين على المادة: | 0 (Anti-Bacterial Agents) |
تواريخ الأحداث: | Date Created: 20220503 Date Completed: 20220616 Latest Revision: 20231109 |
رمز التحديث: | 20231215 |
مُعرف محوري في PubMed: | PMC9197523 |
DOI: | 10.1172/JCI157340 |
PMID: | 35503658 |
قاعدة البيانات: | MEDLINE |
تدمد: | 1558-8238 |
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DOI: | 10.1172/JCI157340 |