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HPV, tumour metabolism and novel target identification in head and neck squamous cell carcinoma

HPV, tumour metabolism and novel target identification in head and neck squamous cell carcinoma
HPV, tumour metabolism and novel target identification in head and neck squamous cell carcinoma
Background: Metabolic changes in tumour cells are used in clinical imaging and may provide potential therapeutic targets. Human papillomavirus (HPV) status is important in classifying head and neck cancers (HNSCC), identifying a tumour subtype with distinct clinical behaviour; metabolic differences between HNSCC subtypes remain poorly understood.
Methods: We used RNA sequencing to classify the metabolic expression profiles of HPV+ve and HPV-ve HNSCC, performed a meta-analysis on FDG-PET imaging characteristics and correlated results with in vitro extracellular flux analysis of HPV-ve and HPV+ve HNSCC cell lines. The monocarboxylic acid transporter-1 (MCT1) was identified as a potential metabolic target and tested in functional assays.
Results: Specific metabolic profiles were associated with HPV status, not limited to carbohydrate metabolism. There was dominance of all energy pathways in HPV-negative disease, with elevated expression of genes associated with glycolysis and oxidative phosphorylation. In vitro analysis confirmed comparative increased rates of oxidative phosphorylation and glycolysis in HPV-negative cell lines. PET SUV(max) scores however were unable to reliably differentiate between HPV-positive and HPV-negative tumours. MCT1 expression was relatively increased in HPV-negative tumours, and inhibition suppressed tumour cell invasion, colony formation and promoted radiosensitivity.
Conclusion: HPV-positive and -negative HNSCC have different metabolic profiles which may have potential therapeutic applications.
0007-0920
356-367
Fleming, Jason
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Woo, Jeongmin
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Moutasim, Karwan
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Mellone, Massimiliano
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Frampton, Steven
a00d94ae-a8ee-4b1a-83ae-fd0ebe08386e
Mead, Abbie
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Ahmed, Waseem
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Wood, Oliver
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Robinson, Hollie
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Ward, Matthew
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Woelk, Christopher H.
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Ottensmeier, Christian
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King, Emma
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Kim, Dae
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Blaydes, Jeremy P.
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Thomas, Gareth
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Fleming, Jason
27877317-4084-43e1-9f50-cc9ed80993b1
Woo, Jeongmin
80c82a2e-810d-49cf-8e75-0ae1e58e2dc1
Moutasim, Karwan
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Mellone, Massimiliano
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Frampton, Steven
a00d94ae-a8ee-4b1a-83ae-fd0ebe08386e
Mead, Abbie
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Ahmed, Waseem
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Wood, Oliver
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Robinson, Hollie
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Ward, Matthew
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Woelk, Christopher H.
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Ottensmeier, Christian
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King, Emma
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Kim, Dae
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Blaydes, Jeremy P.
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Thomas, Gareth
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Fleming, Jason, Woo, Jeongmin, Moutasim, Karwan, Mellone, Massimiliano, Frampton, Steven, Mead, Abbie, Ahmed, Waseem, Wood, Oliver, Robinson, Hollie, Ward, Matthew, Woelk, Christopher H., Ottensmeier, Christian, King, Emma, Kim, Dae, Blaydes, Jeremy P. and Thomas, Gareth (2019) HPV, tumour metabolism and novel target identification in head and neck squamous cell carcinoma. British Journal of Cancer, 120, 356-367. (doi:10.1038/s41416-018-0364-7).

Record type: Article

Abstract

Background: Metabolic changes in tumour cells are used in clinical imaging and may provide potential therapeutic targets. Human papillomavirus (HPV) status is important in classifying head and neck cancers (HNSCC), identifying a tumour subtype with distinct clinical behaviour; metabolic differences between HNSCC subtypes remain poorly understood.
Methods: We used RNA sequencing to classify the metabolic expression profiles of HPV+ve and HPV-ve HNSCC, performed a meta-analysis on FDG-PET imaging characteristics and correlated results with in vitro extracellular flux analysis of HPV-ve and HPV+ve HNSCC cell lines. The monocarboxylic acid transporter-1 (MCT1) was identified as a potential metabolic target and tested in functional assays.
Results: Specific metabolic profiles were associated with HPV status, not limited to carbohydrate metabolism. There was dominance of all energy pathways in HPV-negative disease, with elevated expression of genes associated with glycolysis and oxidative phosphorylation. In vitro analysis confirmed comparative increased rates of oxidative phosphorylation and glycolysis in HPV-negative cell lines. PET SUV(max) scores however were unable to reliably differentiate between HPV-positive and HPV-negative tumours. MCT1 expression was relatively increased in HPV-negative tumours, and inhibition suppressed tumour cell invasion, colony formation and promoted radiosensitivity.
Conclusion: HPV-positive and -negative HNSCC have different metabolic profiles which may have potential therapeutic applications.

Text
Fleming et al., 2018 BJC Accepted version - Accepted Manuscript
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More information

Accepted/In Press date: 28 November 2018
e-pub ahead of print date: 17 January 2019
Published date: 5 February 2019

Identifiers

Local EPrints ID: 426746
URI: https://eprints.soton.ac.uk/id/eprint/426746
ISSN: 0007-0920
PURE UUID: 41271582-3888-45f0-b9a2-708cd0aecbb6
ORCID for Massimiliano Mellone: ORCID iD orcid.org/0000-0002-4964-9340
ORCID for Abbie Mead: ORCID iD orcid.org/0000-0002-1299-8512
ORCID for Jeremy P. Blaydes: ORCID iD orcid.org/0000-0001-8525-0209

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Date deposited: 11 Dec 2018 17:30
Last modified: 26 May 2019 04:01

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