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Intramucosal Inoculation of Squamous Cell Carcinoma Cells in Mice for Tumor Immune Profiling and Treatment Response Assessment
Published on: April 22, 2019
Inhibition of ICAM2 induces radiosensitization in oral squamous cell carcinoma cells
T Ishigami1, K Uzawa, K Fushimi
1Department of Clinical Molecular Biology, Graduate School of Medicine, Chiba University, 1-8-1 Inohana, Chuo-ku, Chiba 260-8670, Japan.
Abstract:
We recently identified genes and molecular pathways related to radioresistance of oral squamous cell carcinoma (OSCC) using Affymetrix GeneChip. The current study focused on the association between one of the target genes, intercellular adhesion molecule 2 (ICAM2), and resistance to X-ray irradiation in OSCC cells, and evaluated the antitumor efficacy of combining ICAM2 small interfering RNA (siRNA) and X-ray irradiation. Downregulation of ICAM2 expression by siRNA enhanced radiosensitivity of OSCC cells with the increased apoptotic phenotype via phosphorylation (ser473) of AKT and activation of caspase-3. Moreover, overexpression of ICAM2 induced greater OSCC cell resistance to the X-ray irradiation with the radioresistance phenotype. These results suggested that ICAM2 silencing is closely related to sensitivity of OSCC cells to radiotherapy, and that ICAM2 may be an effective radiotherapeutic target for this disease.
Insights
Intercellular adhesion molecule 2 (ICAM2) promotes oral squamous cell carcinoma (OSCC) radioresistance. Silencing ICAM2 with small interfering RNA (siRNA) enhances radiosensitivity and antitumor effects in OSCC, suggesting ICAM2 as a therapeutic target.
Area of Science:
- Oncology
- Molecular Biology
- Radiotherapy Research
Background:
- Oral squamous cell carcinoma (OSCC) exhibits radioresistance, a major challenge in radiotherapy.
- Previous studies identified potential genes linked to OSCC radioresistance using gene expression profiling.
Purpose of the Study:
- To investigate the role of intercellular adhesion molecule 2 (ICAM2) in OSCC radioresistance.
- To evaluate the efficacy of combining ICAM2 small interfering RNA (siRNA) with X-ray irradiation for OSCC treatment.
Main Methods:
- Utilized Affymetrix GeneChip for gene identification.
- Employed small interfering RNA (siRNA) to downregulate ICAM2 expression in OSCC cells.
- Assessed radiosensitivity, apoptosis (caspase-3 activation, AKT phosphorylation), and radioresistance phenotypes.
- Investigated the effects of ICAM2 overexpression on radiosensitivity.
Main Results:
- Downregulation of ICAM2 via siRNA significantly enhanced OSCC cell radiosensitivity.
- ICAM2 silencing led to increased apoptosis, evidenced by caspase-3 activation and AKT phosphorylation (ser473).
- Overexpression of ICAM2 conferred greater resistance to X-ray irradiation, demonstrating a radioresistance phenotype.
Conclusions:
- ICAM2 plays a crucial role in mediating radioresistance in oral squamous cell carcinoma.
- ICAM2 silencing enhances sensitivity to radiotherapy, indicating its potential as a therapeutic target.
- Combination therapy of ICAM2 siRNA and X-ray irradiation shows promise for improving OSCC treatment outcomes.
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