ArticleThe American journal of pathology2009
Innate immune cells induce hemorrhage in tumors during thrombocytopenia.
Article in The American journal of pathology, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 62 papers, 1 of them a synthesis that pooled it.
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Who cites it
62 citing papers in PubMed, 1 synthesis or guideline pooled it, 114 citations in OpenAlex.
- Assessment of Prognostic Value of Aspartate Aminotransferase-to-Platelet Ratio Index in Patients With Hepatocellular Carcinoma: Meta-Analysis of 28 Cohort Studies.Frontiers in medicine · 2021Pooled it
- Causal Analysis of Platelet Indices and Breast Cancer, Including Estrogen Receptor-Specific Subtypes: A Mendelian Randomization Study.International journal of women's health · 2025Article
- Preoperative platelet count as an independent predictor of long-term outcomes among patients undergoing resection for intrahepatic cholangiocarcinoma.Journal of surgical oncology · 2024Article
- The importance of blood parameters in the detection of intestinal metaplasia and early diagnosis of gastric cancer.African health sciences · 2024Article
- A multicellular vessel-on-a-chip model reveals context-dependent roles for platelets in inflammation and inflammatory hemostasis.Blood vessels, thrombosis & hemostasis · 2024Article
- The localization, origin, and impact of platelets in the tumor microenvironment are tumor type-dependent.Journal of experimental & clinical cancer research : CR · 2024Article
- The role of platelets in the regulation of tumor growth and metastasis: the mechanisms and targeted therapy.MedComm · 2023Review
- Platelets and (Lymph)angiogenesis.Cold Spring Harbor perspectives in medicine · 2023Review
- The Progress of Platelets in Breast Cancer.Cancer management and research · 2023Review
- Add fuel to the fire: Inflammation and immune response in lung cancer combined with COVID-19.Frontiers in immunology · 2023Review
- Association of Systemic Immune Inflammation Index with All-Cause, Cardiovascular Disease, and Cancer-Related Mortality in Patients with Cardiovascular Disease: A Cross-Sectional Study.Journal of inflammation research · 2023Article
- Procoagulant platelet sentinels prevent inflammatory bleeding through GPIIBIIIA and GPVI.Blood · 2022Article
- Intratumoral Platelets: Harmful or Incidental Bystanders of the Tumor Microenvironment?Cancers · 2022Review
- Application of Regulatory Cell Death in Cancer: Based on Targeted Therapy and Immunotherapy.Frontiers in immunology · 2022Review
- Association of the systemic immune-inflammation index with all-cause mortality in patients with arteriosclerotic cardiovascular disease.Frontiers in cardiovascular medicine · 2022Article
- Impact of Platelets to Lymphocytes Ratio and Lymphocytes during Radical Concurrent Radiotherapy and Chemotherapy on Patients with Nonmetastatic Esophageal Squamous Cell Carcinoma.Journal of oncology · 2022Article
- Role of Cell-Free DNA and Deoxyribonucleases in Tumor Progression.International journal of molecular sciences · 2021Review
- Histone citrullination: a new target for tumors.Molecular cancer · 2021Review
- Platelet-Cancer Interplay: Molecular Mechanisms and New Therapeutic Avenues.Frontiers in oncology · 2021Review
- Article
2 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
6 authors at 1 institution in 2 countries.
Funding
Abstract
Platelets are crucial regulators of tumor vascular homeostasis and continuously prevent tumor hemorrhage through secretion of their granules. However, the reason for tumor bleeding in the absence of platelets remains unknown. Tumors are associated with inflammation, a cause of hemorrhage in thrombocytopenia. Here, we investigated the role of the inflamed tumor microenvironment in the induction of tumor vessel injury in thrombocytopenic mice. Using s.c. injections of vascular endothelial growth factor or tumor necrosis factor-alpha combined with depletion of neutrophils, we demonstrate that enhancing the opening of endothelial cell junctions was not sufficient to cause bleeding in the absence of platelets; instead, induction of tissue hemorrhage in thrombocytopenia required recruitment of leukocytes. Immunohistology revealed that thrombocytopenia-induced tumor hemorrhage occurs at sites of macrophage and neutrophil accumulation. Mice deficient in beta2 or beta3 integrins, which have decreased neutrophil and/or macrophage infiltration in their tumor stroma, were protected from thrombocytopenia-induced tumor hemorrhage, indicating that, in the absence of platelets, stroma-infiltrating leukocytes induced tumor vessel injury. This injury was independent of reactive oxygen species generation and of complement activation, as suggested by the persistence of tumor hemorrhage in C3- and nicotinamide adenine dinucleotide phosphate oxidase-deficient thrombocytopenic mice. Our results show that platelets counteract tumor-associated inflammation and that the absence of this platelet function elicits vascular injuries by tumor-infiltrating innate immune cells.
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