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Therapy Testing in a Spheroid-based 3D Cell Culture Model for Head and Neck Squamous Cell Carcinoma
Published on: April 20, 2018
Identification of molecular targets for immunotherapy of patients with head and neck squamous cell carcinoma
Santanu Dasgupta1, Pulak K Tripathi, Hongxing Qin
1Department of Internal Medicine, the Barrett Cancer Center, University of Cincinnati, Cincinnati, OH 45267, USA.
Abstract:
To identify molecular targets for immunotherapy of head and neck squamous cell carcinoma (HNSCC) patients, we analyzed gene expression profile in matched tumor (HN) and normal fibroblast (FB) cell lines established from a HNSCC patient using microarray technique followed by real-time RT-PCR. Screening against a series of established normal and malignant cell lines followed by screening against a panel of normal human tissues led to the identification of 7 genes (AREG, CDH3, KLK10, NmU, SLPI, ANAX3 and MAL2), which were over-expressed at least 10-fold in tumors over any of the normal tissues. We determined the expression of mRNA encoding these genes against a panel of 15 HNSCC primary tumor samples. Relative expression of these genes was at least 20-fold. Expression of AREG, CDH3, KLK10, NmU and SLPI at the protein level was determined by immunohistochemistry in seven supraglottic laryngeal cancer specimens. All five proteins were expressed in these tumor samples with high intensity. We conclude that these molecules are potential targets for immunotherapy of HNSCC patients.
Insights
Researchers identified seven genes overexpressed in head and neck squamous cell carcinoma (HNSCC) tumors. Five of these genes, AREG, CDH3, KLK10, NmU, and SLPI, were also found at the protein level, indicating potential immunotherapy targets for HNSCC patients.
Area of Science:
- Oncology
- Molecular Biology
- Immunotherapy
Background:
- Head and neck squamous cell carcinoma (HNSCC) is a significant global health concern.
- Identifying novel molecular targets is crucial for developing effective immunotherapies for HNSCC.
Purpose of the Study:
- To identify and validate novel molecular targets for HNSCC immunotherapy.
- To analyze gene and protein expression profiles in HNSCC tumors compared to normal tissues.
Main Methods:
- Gene expression profiling using microarray and real-time RT-PCR.
- Screening of cell lines and normal human tissues to identify overexpressed genes.
- Immunohistochemistry to confirm protein expression in tumor samples.
Main Results:
- Seven genes (AREG, CDH3, KLK10, NmU, SLPI, ANAX3, MAL2) were identified with at least 10-fold overexpression in tumors versus normal tissues.
- mRNA expression of these genes was at least 20-fold higher in HNSCC primary tumors.
- AREG, CDH3, KLK10, NmU, and SLPI proteins were highly expressed in supraglottic laryngeal cancer specimens.
Conclusions:
- The identified genes and their corresponding proteins represent promising molecular targets for HNSCC immunotherapy.
- Further investigation into these targets could lead to the development of new therapeutic strategies for HNSCC patients.
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