ArticleGastric cancer : official journal of the International Gastric Cancer Association and the Japanese Gastric Cancer Association2021
Drug-exposed cancer-associated fibroblasts facilitate gastric cancer cell progression following chemotherapy.
Article in Gastric cancer : official journal of the International Gastric Cancer Association and the Japanese Gastric Cancer Association, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers.
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7 citing papers in PubMed, 14 citations in OpenAlex.
- Cell Biology of Cancer Peritoneal Metastasis: Multiclonal Seeding and Peritoneal Tumor Microenvironment.Cancer science · 2025Review
- Single-cell transcriptomic analysis reveals prognosis-related stromal signatures that potentiate stratification of patients with extrahepatic cholangiocarcinoma.BMC gastroenterology · 2025Article
- Stroma-Mediated Breast Cancer Cell Proliferation Indirectly Drives Chemoresistance by Accelerating Tumor Recovery between Chemotherapy Cycles.Cancer research · 2023Article
- Cancer-associated fibroblast-dependent and -independent invasion of gastric cancer cells.Journal of cancer research and clinical oncology · 2023Article
- Recent progress in molecular mechanisms of postoperative recurrence and metastasis of hepatocellular carcinoma.World journal of gastroenterology · 2022Review
- Cancer-Associated Fibroblasts Influence the Biological Properties of Malignant Tumours via Paracrine Secretion and Exosome Production.International journal of molecular sciences · 2022Review
- IL-6 in the Ecosystem of Head and Neck Cancer: Possible Therapeutic Perspectives.International journal of molecular sciences · 2021Review
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13 authors at 3 institutions in 1 country.
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No grant is acknowledged in the PubMed record.
Abstract
backgroundCancer progression following chemotherapy is a significant barrier to effective cancer treatment. We aimed to evaluate the role of drug-exposed cancer-associated fibroblasts (CAFs) in the growth and progression of drug-exposed gastric cancer (GC) cells and to explore the underlying molecular mechanism.
methodsThe human GC cell line 44As3 and CAFs were treated with 5-fluorouracil and oxaliplatin (5FU + OX). 5FU + OX-pretreated 44As3 cells were then cultured in a conditioned medium (CM) from 5FU + OX-pretreated CAFs, and the growth and migration/invasion ability of the cells were evaluated. We also compared the clinicopathological characteristics of the GC patients treated with S1 + OX in accordance with the properties of their resected specimens, focusing on the number of CAFs. Changes in gene expression in CAFs and 44As3 cells were comprehensively analyzed using RNA-seq analysis.
resultsThe CM from 5FU + OX-pretreated CAFs promoted the migration and invasion of 5FU + OX-pretreated 44As3 cells. Although the number of cases was relatively small (n = 21), the frequency of positive cases of lymphovascular invasion and the recurrence rate were significantly higher in those with more residual CAF. RNA-seq analysis revealed 5FU + OX-pretreated CAF-derived glycoprotein 130 (gp130) as a candidate factor contributing to the increased migration of 5FU + OX-pretreated 44As3 cells. Administration of the gp130 inhibitor SC144 prevented the increased migration ability of 5FU + OX-pretreated 44As3 cells owing to drug-treated CAFs.
conclusionsOur findings provide evidence regarding the interactions between GC cells and CAFs in the tumor microenvironment following chemotherapy, suggesting that ligands for gp130 may be novel therapeutic targets for suppressing or preventing metastasis in GC.
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