ArticleThe Journal of clinical investigation2016
Cancer-associated fibroblast-derived annexin A6+ extracellular vesicles support pancreatic cancer aggressiveness.
Article in The Journal of clinical investigation, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 135 papers, 1 of them a synthesis that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
135 citing papers in PubMed, 1 synthesis or guideline pooled it, 206 citations in OpenAlex.
- Biomarkers of tumor invasiveness in proteomics (Review).International journal of oncology · 2020Pooled it
- Cancer‑associated fibroblast‑derived extracellular vesicles promote pancreatic cancer progression via the RAP1B/ANLN axis.Oncology reports · 2026Article
- Twist1 overexpression models an aggressive subtype of pancreatic ductal adenocarcinoma in vivo.Lab animal · 2026Article
- Review
- Article
- Article
- Exploring the Role of Extracellular Vesicles in Pancreatic and Hepatobiliary Cancers: Advances Through Artificial Intelligence.International journal of molecular sciences · 2026Review
- Modeling CAF-tumor interactions to overcome therapy resistance.Journal of experimental & clinical cancer research : CR · 2026Review
- Role of cancer-associated fibroblast-derived exosomes in pancreatic cancer: clinical therapeutic potential and targeting challenges.Frontiers in immunology · 2026Review
- The Vitamin D3 Analog Calcipotriol Attenuates Pancreatic Cancer Malignancy via Downregulating Thrombospondin 1 in Pancreatic Stellate Cells.Mediators of inflammation · 2026Article
- Unraveling the Role of MDK-SDC4 Interaction in Pancreatic Cancer-Associated New-Onset Diabetes by Single-Cell Transcriptomic Analysis.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Transdifferentiation of tongue muscle cells into cancer-associated fibroblasts in response to tongue squamous cell carcinoma.Nature communications · 2025Article
- Characterization of extracellular vesicle-associated DNA and proteins derived from organotropic metastatic breast cancer cells.Journal of experimental & clinical cancer research : CR · 2025Article
- Small extracellular vesicles (sEVs) in pancreatic cancer progression and diagnosis.Journal of controlled release : official journal of the Controlled Release Society · 2025Review
- Extracellular vesicle signatures from eye lavage as novel non-invasive biomarkers for hypoxic ischaemic insult-findings from a neonatal mouse model.Frontiers in medical technology · 2025Article
- Research Progress of Drug Delivery Systems Consisting of Hydrogels Loaded with Extracellular Vesicles in Tumor Therapy.Oncology research · 2025Review
- 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
- CAFs-Associated Genes (CAFGs) in Pancreatic Ductal Adenocarcinoma (PDAC) and Novel Therapeutic Strategy.International journal of molecular sciences · 2024Review
75 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
23 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The intratumoral microenvironment, or stroma, is of major importance in the pathobiology of pancreatic ductal adenocarcinoma (PDA), and specific conditions in the stroma may promote increased cancer aggressiveness. We hypothesized that this heterogeneous and evolving compartment drastically influences tumor cell abilities, which in turn influences PDA aggressiveness through crosstalk that is mediated by extracellular vesicles (EVs). Here, we have analyzed the PDA proteomic stromal signature and identified a contribution of the annexin A6/LDL receptor-related protein 1/thrombospondin 1 (ANXA6/LRP1/TSP1) complex in tumor cell crosstalk. Formation of the ANXA6/LRP1/TSP1 complex was restricted to cancer-associated fibroblasts (CAFs) and required physiopathologic culture conditions that improved tumor cell survival and migration. Increased PDA aggressiveness was dependent on tumor cell-mediated uptake of CAF-derived ANXA6+ EVs carrying the ANXA6/LRP1/TSP1 complex. Depletion of ANXA6 in CAFs impaired complex formation and subsequently impaired PDA and metastasis occurrence, while injection of CAF-derived ANXA6+ EVs enhanced tumorigenesis. We found that the presence of ANXA6+ EVs in serum was restricted to PDA patients and represents a potential biomarker for PDA grade. These findings suggest that CAF-tumor cell crosstalk supported by ANXA6+ EVs is predictive of PDA aggressiveness, highlighting a therapeutic target and potential biomarker for PDA.
Indexed as
Identifiers
What OpenQuestion holds
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.