ArticleTumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine2016
Macrophages and endothelial cells orchestrate tumor-associated angiogenesis in oral cancer via hedgehog pathway activation.
Article in Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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Who cites it
18 citing papers in PubMed, 26 citations in OpenAlex.
- Hedgehog signaling pathway is an influential factor on vascular biology: a review.Journal of physiology and biochemistry · 2025Review
- Evaluation of Tumor-Associated Macrophages and Micro-Vessel Density in Verrucous Carcinoma and Squamous Cell Carcinoma of the Oral Cavity.Advanced biomedical research · 2024Article
- Interaction between immuno-stem dual lineages in jaw bone formation and injury repair.Frontiers in cell and developmental biology · 2024Review
- The Three-Dimensional In Vitro Cell Culture Models in the Study of Oral Cancer Immune Microenvironment.Cancers · 2023Review
- Review
- Molecular signaling in cancer stem cells of tongue squamous cell carcinoma: Therapeutic implications and challenges.World journal of stem cells · 2023Review
- The role of tumor-associated macrophages in oral squamous cell carcinoma.Frontiers in physiology · 2022Review
- A Synopsis of Signaling Crosstalk of Pericytes and Endothelial Cells in Salivary Gland.Dentistry journal · 2021Review
- The Role of Macrophages in Oral Squamous Cell Carcinoma.Frontiers in oncology · 2021Review
- Hedgehog pathway activation in oral squamous cell carcinoma: cancer-associated fibroblasts exhibit nuclear GLI-1 localization.Journal of molecular histology · 2020Article
- Hedging against Neuropathic Pain: Role of Hedgehog Signaling in Pathological Nerve Healing.International journal of molecular sciences · 2020Review
- Effects of IGF-1 on Proliferation, Angiogenesis, Tumor Stem Cell Populations and Activation of AKT and Hedgehog Pathways in Oral Squamous Cell Carcinoma.International journal of molecular sciences · 2020Article
- CD163Dentistry journal · 2020Article
- LUM Expression and Its Prognostic Significance in Gastric Cancer.Frontiers in oncology · 2020Article
- Role of Hedgehog Signaling in Vasculature Development, Differentiation, and Maintenance.International journal of molecular sciences · 2019Review
- The contribution of tumor-associated macrophages in glioma neo-angiogenesis and implications for anti-angiogenic strategies.Neuro-oncology · 2017Review
- Frontline Science: Shh production and Gli signaling is activated in vivo in lung, enhancing the Th2 response during a murine model of allergic asthma.Journal of leukocyte biology · 2017Article
- Aggressive rat prostate tumors reprogram the benign parts of the prostate and regional lymph nodes prior to metastasis.PloS one · 2017Article
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Authors and funding
7 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The present study aimed to evaluate the role of Hedgehog (Hh) molecule expression in association with the clinical aspects of oral squamous cell carcinoma (OSCC), as well as angiogenesis and CD163+ macrophages. Twenty-eight cases of OSCC, nine cases of tumor-free resection margins (TM), and four cases of non-neoplastic oral mucosa (NNM) were submitted to immunohistochemistry to detect proteins Sonic Hedgehog (SHH), Indian Hedgehog (IHH), GLI1, CD163, and CD105. Protein colocalization with respect to SHH/CD163, IHH/CD163, GLI1/CD163, and GLI1/CD105 was assessed by immunohistochemical double staining. In tumor parenchyma, SHH and IHH were present in the cytoplasm of neoplastic cells, while GLI1 was observed in cytoplasm and nucleus. Endothelial cells were found to express SHH, IHH, and GLI1 within CD105+ vessels, and a positive correlation between infiltrating macrophage density (IMD) and microvascular density (MVD) was observed in cases of OSCC and TM. When compared to TM and NNM, the OSCC cases demonstrated higher immunoreactivity for SHH (p = 0.01), IHH (p = 0.39), GLI1 (p = 0.03), IMD (p = 0.0002), and MVD (p = 0.0002). Our results suggest the participation of the Hh pathway in OSCC by way of autocrine and paracrine signaling, in addition to the participation of both SHH and IHH ligands. Endothelial cells were also found to exhibit positivity with respect to Hh pathway components and we surmise that these molecules may play a role in tumor angiogenesis. CD163+ macrophages were also observed to express IHH, a ligand of this pathway, in addition to being associated with tumor neovascularization.
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