ArticleJournal of experimental & clinical cancer research : CR2021
Integrin alpha-V is an important driver in pancreatic adenocarcinoma progression.
Article in Journal of experimental & clinical cancer research : CR, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 36 papers.
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Who cites it
36 citing papers in PubMed, 72 citations in OpenAlex.
- Therapeutic Efficacy and Safety of Intraperitoneally AdministeredPharmaceutics · 2026Article
- Role of Mechanotransduction in Cancer: A Complex Problem Involving Gene Mutations and Altered Levels of Connection Components.Biomolecules · 2026Review
- Dual-recognizing antibodies targeting CEACAMs in the tumor microenvironment: towards more precise targeting.Cell communication and signaling : CCS · 2026Review
- Selenite modulates phenotype-dependent epithelial-mesenchymal plasticity in pancreatic ductal adenocarcinoma: integrated in vitro analyses and patient-derived ex vivo tissue-slice cultures.Journal of experimental & clinical cancer research : CR · 2026Article
- Improving pancreatic adenocarcinoma prognosis models through ligand receptor interactions and histopathological integration.Journal of translational medicine · 2026Article
- Integrin αvβ3-dependent pathogenic effect and therapeutic effects of DL-N2 combined with EGFR inhibitors in pancreatic adenocarcinoma.Journal of translational medicine · 2026Article
- Downregulation of NFIA facilitates glycolysis, histone lactylation, and activation of the FN1-integrin α5β1 pathway in pancreatic cancer.Apoptosis : an international journal on programmed cell death · 2026Article
- Fibroblast-derived POSTN promotes colorectal cancer progression under high-fat diet by reprogramming fatty acid metabolism in tumor cell.Cell communication and signaling : CCS · 2026Article
- Peritoneal metastasis in pancreatic cancer: molecular mechanisms, microenvironmental remodeling, and emerging intraperitoneal interventions.Frontiers in molecular biosciences · 2026Review
- Multi-omics analysis reveals cell adhesion molecules as key regulators of immune cell infiltration and adverse outcomes and in vitro validation of CLDN16 in pancreatic adenocarcinoma.Cellular and molecular life sciences : CMLS · 2025Article
- The tumour microenvironment in pancreatic cancer - new clinical challenges, but more opportunities.Nature reviews. Clinical oncology · 2025Review
- Exploring the interactions of integrins and CEACAM6 (Review).Experimental and therapeutic medicine · 2025Review
- ITGAV and SMAD4 influence the progression and clinical outcome of pancreatic ductal adenocarcinoma.Molecular oncology · 2025Article
- The regulation of placental pericyte function through transforming growth factor β-1 signalling.Scientific reports · 2025Article
- Emerging therapeutic advancements in pancreatic cancer: a contemporary review.Discover oncology · 2025Review
- miR-3606-3p alleviates skin fibrosis by integratively suppressing the integrin/FAK, p-AKT/p-ERK, and TGF-β signaling cascades.Journal of advanced research · 2025Article
- Integrative multi-omics and machine learning reveal critical functions of proliferating cells in prognosis and personalized treatment of lung adenocarcinoma.NPJ precision oncology · 2025Article
- Interplay of integrins and selectins in metastasis.Molecular oncology · 2025Review
- Spatial Transcriptomics Reveals Novel Mechanisms Involved in Perineural Invasion in Pancreatic Ductal Adenocarcinomas.Cancers · 2025Article
- Systematic analysis of anoikis-related genes identifies SRPX2-FAK/AKT-IL-6 axis in the progression and peritoneal metastasis of gastric cancer.Frontiers in genetics · 2025Article
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Authors and funding
15 authors at 6 institutions in 2 countries.
Funding
Abstract
backgroundMesothelial E- and P-selectins substantially mediate the intraperitoneal spread of Pancreatic ductal adenocarcinoma (PDA) cells in xenograft models. In the absence of selectins in the host, the integrin subunit alpha-V (ITGAV, CD51) was upregulated in the remaining metastatic deposits. Here we present the first experimental study to investigate if ITGAV plays a functional role in PDA tumor growth and progression with a particular focus on intraperitoneal carcinomatosis.
methodsKnockdown of ITGAV was generated using an RNA interference-mediated approach in two PDA cell lines. Tumor growth, intraperitoneal and distant metastasis were analyzed in a xenograft model. Cell lines were characterized in vitro. Gene expression of the xenograft tumors was analyzed. Patient samples were histologically classified and associations to survival were evaluated.
resultsThe knockdown of ITGAV in PDA cells strongly reduces primary tumor growth, peritoneal carcinomatosis and spontaneous pulmonary metastasis. ITGAV activates latent TGF-β and thereby drives epithelial-mesenchymal transition. Combined depletion of ITGAV on the tumor cells and E- and P-selectins in the tumor-host synergistically almost abolishes intraperitoneal spread. Accordingly, high expression of ITGAV in PDA cells was associated with reduced survival in patients.
conclusionCombined depletion of ITGAV in PDA cells and E- and P-selectins in host mice massively suppresses intraperitoneal carcinomatosis of PDA cells xenografted into immunodeficient mice, confirming the hypothesis of a partly redundant adhesion cascade of metastasizing cancer cells. Our data strongly encourage developing novel therapeutic approaches for the combined targeting of E- and P-selectins and ITGAV in PDA.
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