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Updated: May 27, 2026
Three-Dimensional (3D) Tumor Spheroid Invasion Assay
Published on: May 1, 2015
Toll-like receptor 3-mediated tumor invasion in head and neck cancer
Hui-Ching Chuang1, Chao-Cheng Huang, Chih-Yen Chien
1Department of Otolaryngology, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan.
Objectives:
Chronic inflammation associated with some infectious agents can lead to cancer. The Toll-like receptor (TLR) family is one of the largest and best-studied families of pathogen-associated molecular patterns. TLR3 recognizes double-stranded RNA and is a major effector of the immune response against viral pathogens.
Materials And Methods:
We investigated TLR3 protein expression in 153 oral squamous cell carcinoma (OSCC) specimens using tissue microarray. Furthermore, we used polyinosinic-polycytidylic acid (poly I:C) to stimulate head and neck cancer cells and an inhibitor of endosomal acidification bafilomycin A1 to block the TLR 3 signaling pathway to clarify the role of TLR 3 in OSCC.
Results:
Cytoplasmic TLR3 staining was observed in the vast majority of OSCC tissues (73.2%). Strong TLR3 expression was significantly correlated with patients whose tumors were poorly differentiated (P=0.028) and with perineural invasion (P=0.023). Three of the four head and neck cell lines tested (Fadu, OC2, and SCC4) expressed TLR3 mRNA, although at various levels. The stimulation of TLR3-expressing OC2 cells with poly I:C caused the phosphorylation of IFN regulatory factor 3 and IκB and sequentially induced the secretion of interleukin-6 and chemokine (C-C motif) ligand 5 (CCL5) in a dose- and time-dependent manner. Moreover, poly I:C stimulation promoted CCL5-mediated migration in OC2 cells.
Conclusions:
In this report, we provide a novel mechanism for tumor invasion and the TLR3-dependent inflammatory response that could have therapeutic implications for OSCC.
Insights
Toll-like receptor 3 (TLR3) is expressed in oral squamous cell carcinoma (OSCC) and promotes tumor invasion. This TLR3-dependent inflammatory response offers potential therapeutic strategies for OSCC patients.
Area of Science:
- Immunology
- Oncology
- Molecular Biology
Background:
- Chronic inflammation linked to infections can cause cancer.
- Toll-like receptors (TLR) are key in pathogen recognition.
- TLR3 specifically detects double-stranded RNA, crucial for antiviral immunity.
Purpose of the Study:
- To investigate Toll-like receptor 3 (TLR3) protein expression in oral squamous cell carcinoma (OSCC).
- To clarify the role of TLR3 in OSCC pathogenesis and invasion.
- To explore potential therapeutic implications of the TLR3 pathway in OSCC.
Main Methods:
- TLR3 protein expression was analyzed in 153 OSCC specimens using tissue microarray.
- Head and neck cancer cells were stimulated with polyinosinic-polycytidylic acid (poly I:C) to activate TLR3.
- The TLR3 signaling pathway was inhibited using bafilomycin A1 to assess its role.
Main Results:
- Cytoplasmic TLR3 staining was detected in 73.2% of OSCC tissues.
- Strong TLR3 expression correlated with poor differentiation and perineural invasion.
- Poly I:C stimulation induced inflammatory cytokine secretion (IL-6, CCL5) and promoted cancer cell migration.
Conclusions:
- A novel mechanism involving TLR3-dependent inflammation and tumor invasion in OSCC was identified.
- TLR3 signaling plays a significant role in OSCC progression.
- These findings suggest potential therapeutic targets within the TLR3 pathway for OSCC treatment.
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