ArticleCancer discovery2015
Mutant KRAS-induced expression of ICAM-1 in pancreatic acinar cells causes attraction of macrophages to expedite the formation of precancerous lesions.
Article in Cancer discovery, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 138 papers, 1 of them a synthesis that pooled it.
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Who cites it
138 citing papers in PubMed, 1 synthesis or guideline pooled it, 198 citations in OpenAlex.
- Signaling pathway mechanisms in pancreatic ductal adenocarcinoma tumor microenvironment and emerging targeting strategies for improved prognosis.Oncology reviews · 2026Pooled it
- Spatial polarization of endothelial ICAM-1 governs T-cell exclusion in melanoma.EMBO molecular medicine · 2026Article
- Pathophysiological roles of monocytes and macrophages in cancer.Nature reviews. Immunology · 2026Review
- Deciphering the regulatory role of ADAM8 in the PDAC tumor microenvironment.Cellular oncology (Dordrecht, Netherlands) · 2026Article
- Review
- Targeted Therapy in Hepatobiliary Pancreatic Cancer (HPC): Advantages and Advancements of Antibody Drug Conjugates, a Type of Chemo-Biologic Hybrid Drugs.International journal of molecular sciences · 2026Review
- Immunological and molecular insights into acinar-ductal metaplasia and atypical flat lesions as precursor lesions of pancreatic ductal adenocarcinoma.Journal of experimental & clinical cancer research : CR · 2026Article
- Analytical Validation of a Serum Biomarker Signature for Detection of Early-Stage Pancreatic Ductal Adenocarcinoma.Diagnostics (Basel, Switzerland) · 2025Article
- ULK1 knockout suppresses pancreatic cancer progression by inhibiting autophagy and enhancing antitumor immunity.Experimental & molecular medicine · 2025Article
- Downregulation of Sod2 increases atypical flat lesions and dysplasia to advance pancreatic ductal adenocarcinoma.Molecular cancer · 2025Article
- Oncogenic KRAS mutations drive immune suppression through immune-related regulatory network and metabolic reprogramming.Cell death & disease · 2025Review
- Precision immune regulation in KRAS-mutated cancers: the final piece of the puzzle?Journal of experimental & clinical cancer research : CR · 2025Review
- A High Performing Biomarker Signature for Detecting Early-Stage Pancreatic Ductal Adenocarcinoma in High-Risk Individuals.Cancers · 2025Article
- Modulating the CXCR2 Signaling Axis Using Engineered Chemokine Fusion Proteins to Disrupt Myeloid Cell Infiltration in Pancreatic Cancer.Biomolecules · 2025Article
- Pancreatic Cancer: Pathogenesis and Clinical Studies.MedComm · 2025Review
- Cerium-based nanoplatform for severe acute pancreatitis: Achieving enhanced anti-inflammatory effects through calcium homeostasis restoration and oxidative stress mitigation.Materials today. Bio · 2025Article
- Leveraging glycosylation for early detection and therapeutic target discovery in pancreatic cancer.Cell death & disease · 2025Review
- Intercellular TIMP-1-CD63 signaling directs the evolution of immune escape and metastasis in KRAS-mutated pancreatic cancer cells.Molecular cancer · 2025Article
- Coxsackievirus and adenovirus receptor expression facilitates enteroviral infections to drive the development of pancreatic cancer.Nature communications · 2024Article
- FRA1 controls acinar cell plasticity during murine KrasDevelopmental cell · 2024Article
78 more citing papers are in PubMed but not listed here.
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Authors and funding
7 authors at 1 institution in 1 country.
Funding
Abstract
unlabelledDesmoplasia and an inflammatory environment are defining features of pancreatic cancer. Unclear is how pancreatic cells that undergo oncogenic transformation can cross-talk with immune cells and how this contributes to the development of pancreatic lesions. Here, we demonstrate that pancreatic acinar cells expressing mutant KRAS can expedite their transformation to a duct-like phenotype by inducing local inflammation. Specifically, we show that KRAS(G12D) induces the expression of intercellular adhesion molecule-1 (ICAM-1), which serves as chemoattractant for macrophages. Infiltrating macrophages amplify the formation of KRAS(G12D)-caused abnormal pancreatic structures by remodeling the extracellular matrix and providing cytokines such as TNF. Depletion of macrophages or treatment with a neutralizing antibody for ICAM-1 in mice expressing oncogenic Kras under an acinar cell-specific promoter resulted in both a decreased formation of abnormal structures and decreased progression of acinar-to-ductal metaplasia to pancreatic intraepithelial neoplastic lesions. SIGNIFICANCE: We here show that oncogenic KRAS in pancreatic acinar cells upregulates the expression of ICAM-1 to attract macrophages. Hence, our results reveal a direct cooperative mechanism between oncogenic Kras mutations and the inflammatory environment to drive the initiation of pancreatic cancer.
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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.