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Experimental Study: The Development of a Novel Treatment for Chemotherapy-Resistant Tongue Cancer with the Inhibition
Shoji Ikebe1,2, Nobutaka Koibuchi2, Kana Shibata2
1Graduate School of Dentistry (Second Department of Oral and Maxillofacial Surgery), Osaka Dental University, Hirakata 573-1121, Japan.
Abstract:
Tongue squamous cell carcinoma (TSCC) occurs frequently in the oral cavity, and because of its high proliferative and metastatic potential, it is necessary to develop a novel treatment for it. We have reported the importance of the inhibition of the periostin (POSTN) pathological splicing variant, including exon 21 (PN1-2), in various malignancies, but its influence is unclear in tongue cancer. In this study, we investigated the potential of POSTN exon 21-specific neutralizing antibody (PN21-Ab) as a novel treatment for TSCC. Human PN2 was transfected into the human TSCC (HSC-3) and cultured under stress, and PN2 was found to increase cell viability. PN2 induced chemotherapy resistance in HSC-3 via the phosphorylation of the cell survival signal Akt. In tissues from human TSCC and primary tumors of an HSC-3 xenograft model, PN1-2 was expressed in the tumor stroma, mainly from fibroblasts. The intensity of PN1-2 mRNA expression was positively correlated with malignancy. In the HSC-3 xenograft model, CDDP and PN21-Ab promoted CDPP's inhibition of tumor growth. These results suggest that POSTN exon 21 may be a biomarker for tongue cancer and that PN21-Ab may be a novel treatment for chemotherapy-resistant tongue cancer. The treatment points towards important innovations for TSCC, but many more studies are needed to extrapolate the results.
Insights
Periostin (POSTN) exon 21 promotes tongue cancer growth and resistance to chemotherapy. A POSTN exon 21-specific antibody may offer a new treatment strategy for tongue squamous cell carcinoma (TSCC).
Area of Science:
- Oncology
- Molecular Biology
- Cancer Therapeutics
Background:
- Tongue squamous cell carcinoma (TSCC) is an aggressive oral cancer with high metastatic potential, necessitating novel therapeutic approaches.
- The pathological splicing variant of periostin (POSTN), specifically including exon 21 (PN1-2), has been implicated in various malignancies, but its role in TSCC remains largely uncharacterized.
Purpose of the Study:
- To investigate the role of POSTN exon 21 in TSCC.
- To evaluate the therapeutic potential of a POSTN exon 21-specific neutralizing antibody (PN21-Ab) for TSCC treatment.
Main Methods:
- Transfection of human PN2 into human TSCC (HSC-3) cells and culture under stress.
- Assessment of cell viability and chemotherapy resistance.
- Analysis of PN1-2 expression in human TSCC tissues and an HSC-3 xenograft model.
- Evaluation of PN21-Ab efficacy in combination with cisplatin (CDDP) in the HSC-3 xenograft model.
Main Results:
- PN2 expression increased cell viability and induced chemotherapy resistance in HSC-3 cells via Akt signaling.
- PN1-2 was predominantly expressed in the tumor stroma of TSCC and correlated positively with malignancy.
- PN21-Ab, in combination with CDDP, enhanced tumor growth inhibition in the HSC-3 xenograft model.
Conclusions:
- POSTN exon 21 may serve as a valuable biomarker for tongue cancer.
- PN21-Ab demonstrates potential as a novel therapeutic agent for chemotherapy-resistant TSCC.
- Further research is warranted to validate these findings and explore clinical applications.
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