ArticleJournal of cellular and molecular medicine2019
Complement C3a promotes proliferation, migration and stemness in cutaneous squamous cell carcinoma.
Article in Journal of cellular and molecular medicine, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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Who cites it
17 citing papers in PubMed, 34 citations in OpenAlex.
- Insulin Resistance and Cutaneous Squamous Cell Carcinoma: A Narrative Review of Molecular Mechanisms.Iranian journal of medical sciences · 2026Review
- The insider's perspective: The intracellular complosome and immune cell dynamics in cancer.Clinical and translational medicine · 2026Review
- Complement system in tumor growth and metastases.British journal of cancer · 2026Review
- Deciphering the role of complement system genes in pancreatic cancer susceptibility and prognosis.Nature communications · 2025Article
- Review
- Molecular Alterations in Cutaneous Squamous Cell Carcinoma in Immunocompetent and Immunosuppressed Hosts-A Systematic Review.Cancers · 2023Review
- Wnt Signaling Pathways: From Inflammation to Non-Melanoma Skin Cancers.International journal of molecular sciences · 2023Review
- Association of plasma MMP-2 levels and prognosis of patients with intracerebral hemorrhage: a prospective cohort study.Frontiers in neurology · 2023Article
- An update on the role of complement in hepatocellular carcinoma.Frontiers in immunology · 2022Review
- Inside-Out of Complement in Cancer.Frontiers in immunology · 2022Review
- Freeze-Dried Secretome (Lyosecretome) from Mesenchymal Stem/Stromal Cells Promotes the Osteoinductive and Osteoconductive Properties of Titanium Cages.International journal of molecular sciences · 2021Article
- Review
- Complement and Cancer-A Dysfunctional Relationship?Antibodies (Basel, Switzerland) · 2020Review
- Transcriptomic analysis reveals dynamic molecular changes in skin induced by mechanical forces secondary to tissue expansion.Scientific reports · 2020Article
- Activated Hepatic Stellate Cells (HSCs) Exert Immunosuppressive Effects in Hepatocellular Carcinoma by Producing Complement C3.OncoTargets and therapy · 2020Article
- Context-dependent roles of complement in cancer.Nature reviews. Cancer · 2019Review
- Complement C3a promotes proliferation, migration and stemness in cutaneous squamous cell carcinoma.Journal of cellular and molecular medicine · 2019Article
Corrections and comments
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Authors and funding
4 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundComplement C3 has been shown to be highly expressed in cutaneous squamous cell carcinoma (cSCC) tumour tissues and is correlated with tumour cell growth. This study aimed to investigate the mechanism of C3 in cSCC malignant transformation.
methodsC3 expression was analysed in cSCC cell lines A431, Tca8113, SCC13, HSC-5 and HSC-1 and in immortalized HaCaT keratinocytes. Proliferation and migration of cSCC were determined after C3a exposure. Expression of cyclin D1, cyclin E, vascular endothelial growth factor (VEGF), pro-matrix metalloproteinase 1 (pro-MMP1), pro-matrix metalloproteinase 2 (pro-MMP2), stemness factors, GSK-3β, and β-catenin were analyzed. Tumour growth was examined in a murine xenograft model.
resultsC3 expression was much more highly expressed in all cSCC cell lines than in HaCaT cells. C3a treatment significantly promoted cSCC cell proliferation and migration and upregulated cyclin D1, cyclin E, VEGF, pro-MMP1 and pro-MMP2 expression, which were impeded by the C3aR antagonist. Moreover, the expression of stemness factors Sox-2, Nanog, Oct-4, c-Myc and CD-44 was stimulated by C3a and slowed by C3aR disruption. Knockdown of Sox-2 by siRNA transfection suppressed cell proliferation and migration, constrained VEGF secretion and inhibited pro-MMP1 and pro-MMP2 expression. C3a also activated the Wnt and β-catenin pathway in cSCC cells. Disruption of C3aR expression dampened tumour growth and the expression of Wnt-1, β-catenin and Sox-2 in the xenograft model.
conclusionsC3a enhanced cell proliferation, migration and stemness in cSCC, and this activity was correlated with activation of the Wnt and β-catenin pathway.
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