ArticleOncogenesis2023
Fibroblasts in metastatic lymph nodes confer cisplatin resistance to ESCC tumor cells via PI16.
Article in Oncogenesis, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers.
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The trial behind it
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Who cites it
9 citing papers in PubMed, 10 citations in OpenAlex.
- Myofibroblast-Like CAFs in Metastatic Lymph Nodes Drive Tumor Stemness and Poor Prognosis in Head and Neck Cancer.Cancer science · 2026Article
- Integrating multi-omics and machine learning to unravel mechanisms of lymph node metastasis in papillary carcinoma with and without thyroiditis.Frontiers in immunology · 2026Article
- Integrated Bulk and Single-Cell Transcriptomic Analyses Identify a Five-Gene Signature Associated With Prognosis and the Tumor Microenvironment in Epstein-Barr Virus-Associated Gastric Cancer.Genetics research · 2026Article
- Overcoming chemoresistance in esophageal cancer with synergistic strategies.Frontiers in immunology · 2026Review
- Fibroblast-derived PI16 enhances tumor immune-suppressive microenvironment via inducing Tregs differentiation.Cellular oncology (Dordrecht, Netherlands) · 2025Article
- Single-cell analyses reveal metastasis mechanism and microenvironment remodeling of lymph node in intrahepatic cholangiocarcinoma.JHEP reports : innovation in hepatology · 2025Article
- Reference gene evaluation for normalization of gene expression studies with lymph tissue and node‑derived stromal cells of patients with oral squamous cell carcinoma.Oncology letters · 2024Article
- Decreased plasma gelsolin fosters a fibrotic tumor microenvironment and promotes chemoradiotherapy resistance in esophageal squamous cell carcinoma.Journal of biomedical science · 2024Article
- The complex interplay of tumor-infiltrating cells in driving therapeutic resistance pathways.Cell communication and signaling : CCS · 2024Review
Corrections and comments
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Authors and funding
9 authors at 1 institution in 2 countries.
Funding
Abstract
Although many studies have compared tumor fibroblasts (T-Fbs) and nontumor fibroblasts (N-Fbs), less is understood about the stromal contribution of metastatic lymph node fibroblasts (LN-Fbs) to the evolving microenvironment. Here, we explored the characteristics of LN-Fbs in esophageal squamous cell carcinoma (ESCC) and the interactions between fibroblasts and ESCC tumor cells in metastatic lymph nodes. Fibroblasts were isolated from tumor, nontumor and metastatic lymph node tissues from different patients with ESCC. Transcriptome sequencing was performed on the fibroblasts. Tumor growth and drug-resistance assays were carried out, and characteristics of T-Fbs, N-Fbs and LN-Fbs were determined. Liquid chromatography-tandem mass spectrometry (LC-MS/MS) was used to assay the culture medium of fibroblasts. The results demonstrated that fibroblasts derived from different tissues had different characteristics. Coculture with LN-Fbs conditioned medium inhibited ESCC tumor cell growth and induced chemoresistance in ESCC cells. LN-Fbs induced chemoresistance to cisplatin in ESCC cells by secreting PI16. Coculture with LN-Fbs conditioned medium decreased cisplatin-induced apoptosis in ESCC cells by regulating the p38 and JNK cell signaling pathways. Survival analyses showed that patients with high PI16 expression in Fbs of lymph nodes exhibited worse overall survival. We also examined PI16 expression in interstitial tissues in ESCC tumor samples of patients receiving platinum-based therapy postsurgery and found that high PI16 expression in tumor interstitial tissues was an independent prognostic factor for ESCC patients. In addition, an in vivo assay demonstrated that PI16 knockdown increased the sensitivity of ESCC cells to cisplatin. Our results suggest that fibroblasts in metastatic lymph nodes decrease apoptosis of ESCC cells via PI16, thereby providing a cisplatin-resistance niche and supporting ESCC tumor cells to survive in metastatic lymph nodes. PI16 is also a potential target for effectively blocking the chemoresistance niche signaling circuit in response to cisplatin.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.