ArticleOncotarget2015
Elevated S100A9 expression in tumor stroma functions as an early recurrence marker for early-stage oral cancer patients through increased tumor cell invasion, angiogenesis, macrophage recruitment and interleukin-6 production.
Article in Oncotarget, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.
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Who cites it
26 citing papers in PubMed, 27 citations in OpenAlex.
- S100A9 regulates eosinophil extracellular trap and activates NF-κB signaling in endometrial cancer: a machine learning-based biomarker discovery.Cancer cell international · 2025Article
- Metastatic Melanoma Treatment and Prophylaxis with S100A9-Targeting Cowpea Mosaic Virus Nanoparticles.Methods in molecular biology (Clifton, N.J.) · 2025Article
- Characterization of Immunosuppressive Myeloid Cells in Merkel Cell Carcinoma: Correlation with Resistance to PD-1 Pathway Blockade.Clinical cancer research : an official journal of the American Association for Cancer Research · 2024Article
- Blocking S100A9-signaling is detrimental to the initiation of anti-tumor immunity.Frontiers in immunology · 2024Article
- Viral nanoparticle vaccines against S100A9 reduce lung tumor seeding and metastasis.Proceedings of the National Academy of Sciences of the United States of America · 2023Article
- Dialog beyond the Grave: Necrosis in the Tumor Microenvironment and Its Contribution to Tumor Growth.International journal of molecular sciences · 2023Review
- BAL Proteomic Signature of Lung Adenocarcinoma in IPF Patients and Its Transposition in Serum Samples for Less Invasive Diagnostic Procedures.International journal of molecular sciences · 2023Article
- The functions and regulatory pathways of S100A8/A9 and its receptors in cancers.Frontiers in pharmacology · 2023Review
- 4-nitroquinoline 1-oxide induces immune cells death to onset early immunosuppression during oral squamous cell carcinoma development.Frontiers in immunology · 2023Article
- Metastatic Colon Cancer Treatment Using S100A9-Targeted Cowpea Mosaic Virus Nanoparticles.Biomacromolecules · 2022Article
- Overexpression of S100A9 in tumor stroma contribute to immune evasion of NK/T cell lymphoma and predict poor response rate.Scientific reports · 2021Article
- The Role of Macrophages in Oral Squamous Cell Carcinoma.Frontiers in oncology · 2021Review
- Diverse roles of bitter melon (Journal of cancer metastasis and treatment · 2021Article
- Baseline and Disease-Induced Transcriptional Profiles in Children with Sickle Cell Disease.Scientific reports · 2020Article
- S100 Calcium Binding Protein A9 Represses Angiogenic Activity and Aggravates Osteonecrosis of the Femoral Head.International journal of molecular sciences · 2019Article
- Long-Term Exposure to Oroxylin A Inhibits Metastasis by Suppressing CCL2 in Oral Squamous Cell Carcinoma Cells.Cancers · 2019Article
- Review
- Bitter Melon Prevents the Development of 4-NQO-Induced Oral Squamous Cell Carcinoma in an Immunocompetent Mouse Model by Modulating Immune Signaling.Cancer prevention research (Philadelphia, Pa.) · 2018Article
- Expression of small leucine-rich extracellular matrix proteoglycans biglycan and lumican reveals oral lichen planus malignant potential.Clinical oral investigations · 2018Article
- Downregulation of Calcium-Binding Protein S100A9 Inhibits Hypopharyngeal Cancer Cell Proliferation and Invasion Ability Through Inactivation of NF-κB Signaling.Oncology research · 2017Article
Corrections and comments
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Authors and funding
11 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
S100A9 is a calcium-binding protein with two EF-hands and frequently deregulated in several cancer types, however, with no clear role in oral cancer. In this report, the expression of S100A9 in cancer and adjacent tissues from 79 early-stage oral cancer patients was detected by immunohistochemical staining. Although S100A9 protein was present in both tumor and stromal cells, only the early-stage oral cancer patients with high stromal expression had reduced recurrence-free survival. High stromal S100A9 expression was also significantly associated with non-well differentiation and recurrence. In addition to increasing cell migration and invasion, ectopic S100A9 expression in tumor cells promoted xenograft tumorigenesis as well as the dominant expression of myeloid cell markers and pro-inflammatory IL-6. The expression of S100A9 in one stromal component, monocytes, stimulated the aggressiveness of co-cultured oral cancer cells. We also detected the elevation of serum S100A9 levels in early-stage oral cancer patients of a separate cohort of 73 oral cancer patients. The release of S100A9 protein into extracellular milieu enhanced tumor cell invasion, transendothelial monocyte migration and angiogenic activity. S100A9-mediated release of IL-6 requires the crosstalk of tumor cells with monocytes through the activation of NF-κB and STAT-3. Early-stage oral cancer patients with both high S100A9 expression and high CD68+ immune infiltrates in stroma had shortest recurrence-free survival, suggesting the use of both S100A9 and CD68 as poor prognostic markers for oral cancer. Together, both intracellular and extracellular S100A9 exerts a tumor-promoting action through the activation of oral cancer cells and their associated stroma in oral carcinogenesis.
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