ArticleCancer discovery2024
Tumor Explants Elucidate a Cascade of Paracrine SHH, WNT, and VEGF Signals Driving Pancreatic Cancer Angiosuppression.
Article in Cancer discovery, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
What it found
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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.
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Who cites it
17 citing papers in PubMed, 20 citations in OpenAlex.
- The role of protein palmitoylation in disease pathogenesis and therapeutic innovation.Annals of medicine · 2026Review
- Fibroblasts: a diverse population of cells balancing homeostasis, wound healing, regeneration, inflammation, fibrosis, and cancer across organs.JCI insight · 2026Review
- Heterocellular crosstalk and architecture of the pancreatic tumour microenvironment.Nature reviews. Cancer · 2026Review
- Responsive nanomedicine strategies achieve pancreatic cancer precise theranostics.Bioactive materials · 2026Review
- Tumor Microenvironment-Responsive Nanoparticles for Pancreatic Cancer Imaging and Treatment.International journal of nanomedicine · 2026Review
- The tumour microenvironment in pancreatic cancer - new clinical challenges, but more opportunities.Nature reviews. Clinical oncology · 2025Review
- Review
- An injury-associated lobular microniche is associated with the classical tumor cell phenotype in pancreatic cancer.Nature communications · 2025Article
- Tumor nutrient stress gives rise to a drug tolerant cell state in pancreatic cancer.bioRxiv : the preprint server for biology · 2025Article
- Experimental models of pancreas cancer: what has been the impact for precision medicine?The Journal of clinical investigation · 2025Review
- Hydrogel-Mediated Preservation of Live Tumor Explants for Drug Development in Peritoneal Metastases.Advanced materials (Deerfield Beach, Fla.) · 2025Article
- What's on the menu?: metabolic constraints in the pancreatic tumor microenvironment.The Journal of clinical investigation · 2025Review
- Ras-dependent activation of BMAL2 regulates hypoxic metabolism in pancreatic cancer.bioRxiv : the preprint server for biology · 2025Article
- CAFs vs. TECs: when blood feuds fuel cancer progression, dissemination and therapeutic resistance.Cellular oncology (Dordrecht, Netherlands) · 2024Review
- Article
- Imperatorin Suppresses Aberrant Hedgehog Pathway and Overcomes Smoothened Antagonist Resistance via STAT3 Inhibition.Drug design, development and therapy · 2024Article
- Mismatch repair-proficient tumor footprints in the sands of immune desert: mechanistic constraints and precision platforms.Frontiers in immunology · 2024Review
Corrections and comments
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Authors and funding
19 authors at 5 institutions in 3 countries.
Funding
Abstract
The sparse vascularity of pancreatic ductal adenocarcinoma (PDAC) presents a mystery: What prevents this aggressive malignancy from undergoing neoangiogenesis to counteract hypoxia and better support growth? An incidental finding from prior work on paracrine communication between malignant PDAC cells and fibroblasts revealed that inhibition of the Hedgehog (HH) pathway partially relieved angiosuppression, increasing tumor vascularity through unknown mechanisms. Initial efforts to study this phenotype were hindered by difficulties replicating the complex interactions of multiple cell types in vitro. Here we identify a cascade of paracrine signals between multiple cell types that act sequentially to suppress angiogenesis in PDAC. Malignant epithelial cells promote HH signaling in fibroblasts, leading to inhibition of noncanonical WNT signaling in fibroblasts and epithelial cells, thereby limiting VEGFR2-dependent activation of endothelial hypersprouting. This cascade was elucidated using human and murine PDAC explant models, which effectively retain the complex cellular interactions of native tumor tissues. SIGNIFICANCE: We present a key mechanism of tumor angiosuppression, a process that sculpts the physiologic, cellular, and metabolic environment of PDAC. We further present a computational and experimental framework for the dissection of complex signaling cascades that propagate among multiple cell types in the tissue environment. This article is featured in Selected Articles from This Issue, p. 201.
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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.