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The Ohio State University

1. supsavhad, wachiraphan. Novel Molecular Targets for Feline Oral Squamous Cell Carcinoma.

Degree: PhD, Comparative and Veterinary Medicine, 2016, The Ohio State University

Feline oral squamous cell carcinoma (FOSCC) is the most common oral cancer in cats. This cancer is very aggressive and has the ability to invade into the adjacent bone resulting in poor quality of life and a grave prognosis in affected cats. FOSCC has been shown to be comparable to human OSCC in many aspects. However, the pathogenesis of FOSCC remains unclear. Similar to human OSCC, FOSCCs respond poorly to the available standard therapy. Therefore, novel molecular targets as well as effective therapies are required for this cancer. The usefulness of p16, p53, and pRb immunohistochemistry (IHC) for human OSCC classification has been reported. Low p16 frequently associates with non-viral-associated OSCCs, while high p16 with low p53 and pRb usually occurs in HPV-associated OSCC. In addition, a favorable prognosis was found in patients with HPV-associated OSCC and a grave prognosis was observed in patients with non-viral-associated OSCC. In this study, the IHC pattern of p16, p53, and pRb in FOSCC was investigated. We found that low p16 IHC is common in FOSCCs and high p16 IHC is present in a subset of patients with this cancer. However feline papillomavirus was not detected in these samples. These results indicate that FOSCCs have more than one type of classification and a variation in pathogenesis may occur in FOSCC.Increased osteoprotegerin (OPG) has been found to reduce tumor size and bone invasion in many human bone-invasive cancers. Low levels of feline OPG (fOPG) mRNA expression were previously observed in a bone-invasive FOSCC cell line (SCCF2). The role of fOPG in bone-invasive FOSCC in vitro and in vivo was investigated using a novel bone-invasive FOSCC cell line with high fOPG mRNA expression (SCCF2-OPGv.1).We found that overexpression of fOPG reduced tumor growth and inhibited bone invasion in bone-invasive FOSCC in vivo. Thus, fOPG could be effective adjuvant therapy for FOSCC-associated bone lysis. Telomerase, a protein complex with cell immortalization activity, has been speculated as a novel therapeutic target for human cancers. Telomerase transcriptase catalytic subunit (TERT) and the non-coding RNA template are the main components of this protein. Pre-mRNA alternative splicing occurs in human TERT gene and more than 20 human TERT alternative splice variants were identified. In this study, high levels of telomerase activity were observed in FOSCC cells (SCCF1, SCCF2, and SCCF3) and in 2 of 3 FOSCC tumors. Full-length and 10 novel feline TERT (fTERT) alternative splice variants were identified. Full-length and the deletion of exon 10 (Del-e10) splice variant of fTERT were the two common variants in FOSCCs with high telomerase activity found in this study. These findings suggest that alternative splicing is important for the regulation of telomerase activity and provide critical information to further the understanding of telomerase in feline cancers. Advisors/Committee Members: Rosol, Thomas (Advisor).

Subjects/Keywords: Molecular Biology; Veterinary Services; Animal Diseases; Experiments; Feline; oral squamous cell carcinoma; FOSCC; animal model; IHC; p16; p53; pRb; osteoprotegerin; OPG; bone-invasive cancers; telomerase; TERT; alternative splicing; cloning

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APA (6th Edition):

supsavhad, w. (2016). Novel Molecular Targets for Feline Oral Squamous Cell Carcinoma. (Doctoral Dissertation). The Ohio State University. Retrieved from http://rave.ohiolink.edu/etdc/view?acc_num=osu1471628009

Chicago Manual of Style (16th Edition):

supsavhad, wachiraphan. “Novel Molecular Targets for Feline Oral Squamous Cell Carcinoma.” 2016. Doctoral Dissertation, The Ohio State University. Accessed May 09, 2021. http://rave.ohiolink.edu/etdc/view?acc_num=osu1471628009.

MLA Handbook (7th Edition):

supsavhad, wachiraphan. “Novel Molecular Targets for Feline Oral Squamous Cell Carcinoma.” 2016. Web. 09 May 2021.

Vancouver:

supsavhad w. Novel Molecular Targets for Feline Oral Squamous Cell Carcinoma. [Internet] [Doctoral dissertation]. The Ohio State University; 2016. [cited 2021 May 09]. Available from: http://rave.ohiolink.edu/etdc/view?acc_num=osu1471628009.

Council of Science Editors:

supsavhad w. Novel Molecular Targets for Feline Oral Squamous Cell Carcinoma. [Doctoral Dissertation]. The Ohio State University; 2016. Available from: http://rave.ohiolink.edu/etdc/view?acc_num=osu1471628009

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