ArticleCell communication and signaling : CCS2025
Fusobacterium nucleatum-reprogrammed adipocytes promote tumor cisplatin resistance through the CCL2-CCR2 axis in the necrotic metastatic neck nodes of head and neck carcinoma.
Article in Cell communication and signaling : CCS, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.
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1 citing paper in PubMed.
- The chemokine network in triple-negative breast cancer: its role in immune microenvironment regulation, and prospects for targeted therapy.Frontiers in immunology · 2026Review
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Abstract
backgroundNecrosis plays a pivotal role in the development of cisplatin resistance in metastatic neck lymph nodes of head and neck squamous cell carcinoma (HNSCC). However, the precise mechanisms underlying this association remain unclear.
methodsWe employed qPCR and DNA in situ hybridization to detect Fusobacterium nucleatum (F. nucleatum) in postoperative tissue specimens from node-positive HNSCC patients. Transcriptomic sequencing was performed to analyze gene expression changes in adipocytes following F. nucleatum co-culture. RNA and protein expression alterations were validated via qPCR, Western blot, and ELISA. Additionally, subcutaneous xenograft tumor models were utilized for in vivo validation.
resultsF. nucleatum was found to preferentially colonize necrotic neck lymph nodes in HNSCC and infiltrate adjacent adipocytes. In vitro, F. nucleatum induced the formation of cancer-associated adipocytes via autocrine C-C motif chemokine ligand 2 (CCL2), which stimulated lipolysis and enhanced free fatty acid release. Paracrine CCL2 further drove glutathione accumulation and cisplatin resistance in HNSCC by upregulating solute carrier family 1 member 5 (SLC1A5) and solute carrier family 7 member 11 (SLC7A11). Notably, C-C chemokine receptor type 2 (CCR2) antagonist, RS504393, effectively reversed these F. nucleatum-mediated pro-tumor effects. In vivo studies further confirmed the role of F. nucleatum-reprogrammed adipocytes and the therapeutic potential of RS504393.
conclusionThis study is the first to elucidate the crucial involvement of F. nucleatum in shaping cancer-associated adipocytes within the HNSCC microenvironment. F. nucleatum-reprogrammed adipocytes enhance cisplatin resistance via the CCL2-CCR2 axis, offering new therapeutic avenues to overcome chemotherapy resistance in necrotic neck lymph nodes.
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