ArticleCancers2022
Cancer-Associated Fibroblasts Confer Gemcitabine Resistance to Pancreatic Cancer Cells through PTEN-Targeting miRNAs in Exosomes.
Article in Cancers, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 38 papers.
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Who cites it
38 citing papers in PubMed, 55 citations in OpenAlex.
- Cancer‑associated fibroblast‑derived extracellular vesicles promote pancreatic cancer progression via the RAP1B/ANLN axis.Oncology reports · 2026Article
- Liquid Biopsy-Derived microRNAs in Pancreatic Ductal Adenocarcinoma: Matrix-Specific Evidence and Translational Challenges.International journal of molecular sciences · 2026Review
- Review
- Role of cancer-associated fibroblast-derived exosomes in pancreatic cancer: clinical therapeutic potential and targeting challenges.Frontiers in immunology · 2026Review
- Extracellular Vesicles in Pancreatic Cancer Function and Potential Clinical Applications.OncoTargets and therapy · 2026Review
- Reversible chemoresistance of pancreatic cancer grown as spheroids.Journal of chemotherapy (Florence, Italy) · 2025Article
- Decoding the pancreatic cancer microenvironment: The multifaceted regulation of microRNAs.Clinical and translational medicine · 2025Review
- Cancer-associated fibroblast-derived COL17A1 promotes gemcitabine resistance and tumorigenesis in pancreatic cancer cells by interacting with ACTN4.Discover oncology · 2025Article
- Exosomes: their role and therapeutic potential in overcoming drug resistance of gastrointestinal cancers.Frontiers in oncology · 2025Review
- Domestication and feedback: bidirectional hijacking in pancreatic ductal adenocarcinoma microenvironment.Frontiers in immunology · 2025Review
- Extracellular vesicles-derived extracellular RNA in bladder cancer: current progress and future prospects.Therapeutic advances in medical oncology · 2025Review
- Article
- Review
- Recent Advances of Small Extracellular Vesicles for the Regulation and Function of Cancer-Associated Fibroblasts.International journal of molecular sciences · 2024Review
- Cancer therapy resistance mediated by cancer-associated fibroblast-derived extracellular vesicles: biological mechanisms to clinical significance and implications.Molecular cancer · 2024Review
- Pancreatic cancer cell- and cancer-associated fibroblast-derived exosomes in disease progression, metastasis, and therapy.Discover oncology · 2024Review
- SNHG4-mediated PTEN destabilization confers oxaliplatin resistance in colorectal cancer cells by inhibiting ferroptosis.Apoptosis : an international journal on programmed cell death · 2024Article
- miRNAs in pancreatic cancer progression and metastasis.Clinical & experimental metastasis · 2024Review
- Review
- A Current Synopsis of the Emerging Role of Extracellular Vesicles and Micro-RNAs in Pancreatic Cancer: A Forward-Looking Plan for Diagnosis and Treatment.International journal of molecular sciences · 2024Review
Corrections and comments
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Authors and funding
4 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Pancreatic ductal adenocarcinoma (PDAC) is currently the third leading cause of cancer-related death in the United States. Even though the poor prognosis of PDAC is often attributed to late diagnosis, patients with an early diagnosis who undergo tumor resection and adjuvant chemotherapy still show tumor recurrence, highlighting a need to develop therapies which can overcome chemoresistance. Chemoresistance has been linked to the high expression of microRNAs (miRs), such as miR-21, within tumor cells. Tumor cells can collect miRs through the uptake of miR-containing lipid extracellular vesicles called exosomes. These exosomes are secreted in high numbers from cancer-associated fibroblasts (CAFs) within the tumor microenvironment during gemcitabine treatment and can contribute to cell proliferation and chemoresistance. Here, we show a novel mechanism in which CAF-derived exosomes may promote proliferation and chemoresistance, in part, through suppression of the tumor suppressor PTEN. We identified five microRNAs: miR-21, miR-181a, miR-221, miR-222, and miR-92a, that significantly increased in number within the CAF exosomes secreted during gemcitabine treatment which target PTEN. Furthermore, we found that CAF exosomes suppressed PTEN expression in vitro and that treatment with the exosome inhibitor GW4869 blocked PTEN suppression in vivo. Collectively, these findings highlight a mechanism through which the PTEN expression loss, often seen in PDAC, may be attained and lend support to investigations into the use of exosome inhibitors as potential therapeutics to improve the effectiveness of chemotherapy.
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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.