Fatty acid synthase as a potential therapeutic target in feline oral squamous cell carcinoma

J. Z. Walz, J. Saha, A. Arora, A. Khammanivong, M. G. O'Sullivan, E. B. Dickerson

Research output: Contribution to journalArticlepeer-review

5 Scopus citations

Abstract

Oral squamous cell carcinoma (OSCC) is an aggressive and treatment-resistant malignancy in both feline and human patients. Recent work has demonstrated aberrant expression of fatty acid synthase (FASN) and an increased capacity for lipogenesis in human OSCC and other cancers. In human OSCC, inhibition of FASN decreased cell viability and growth in vitro, and diminished tumour growth and metastasis in murine preclinical models. This study aimed to characterize FASN as a therapeutic target in feline OSCC. Immunohistochemistry revealed high FASN expression in primary feline OSCC tumours, and FASN expression was detected in OSCC cell lines (3 feline and 3 human) by immunoblotting and quantitative real-time-polymerase chain reaction (qRT-PCR). Orlistat, a FASN inhibitor, substantially reduced cell viability in both feline and human OSCC lines, although feline cell lines consistently displayed higher sensitivity to the drug. FASN mRNA expression among cell lines mirrored sensitivity to orlistat, with feline cell lines expressing higher levels of FASN. Consistent with this observation, diminished sensitivity to orlistat treatment and decreased FASN mRNA expression were observed in feline OSCC cells following incubation under hypoxic conditions. Treatment with orlistat did not potentiate sensitivity to carboplatin in the cell lines investigated; instead, combinations of the 2 drugs resulted in additive to antagonistic effects. Our results suggest that FASN inhibition is a viable therapeutic target for feline OSCC. Furthermore, cats may serve as a spontaneous large animal model for human oral cancer, although differences in the regulation of lipogenesis between these 2 species require further investigation.

Original languageEnglish (US)
Pages (from-to)E99-E108
JournalVeterinary and Comparative Oncology
Volume16
Issue number1
DOIs
StatePublished - Mar 2018

Bibliographical note

Funding Information:
The authors wish to acknowledge Drs Derek Korpela and Amelia Campbell for their contributions and technical knowledge, and thank Ms Paula Overn for her excellent technical expertise. The authors also wish to extend their gratitude to Drs Craig Miller and Sue Van-deWoude (Colorado State University) for providing samples of normal feline oral tissue. This work was supported by funding from the University of Minnesota College of Veterinary Medicine Small Companion Animal Grant (J.Z.W. and E.B.D.). A portion of this research was presented in abstract form at the Veterinary Cancer Society Annual Meeting, Tampa, Florida, October 2016.

Funding Information:
The authors wish to acknowledge Drs Derek Korpela and Amelia Campbell for their contributions and technical knowledge, and thank Ms Paula Overn for her excellent technical expertise. The authors also wish to extend their gratitude to Drs Craig Miller and Sue VandeWoude (Colorado State University) for providing samples of normal feline oral tissue. This work was supported by funding from the University of Minnesota College of Veterinary Medicine Small Companion Animal Grant (J.Z.W. and E.B.D.). A portion of this research was presented in abstract form at the Veterinary Cancer Society Annual Meeting, Tampa, Florida, October 2016.

Keywords

  • cancer metabolism
  • comparative oncology
  • oral neoplasia
  • targeted therapy
  • tumour biology

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