Phosphodiesterase type 5 inhibitors enhance chemotherapy in preclinical models of esophageal adenocarcinoma by targeting cancer-associated fibroblasts

Accepted/In Press date: 28 January 2022

e-pub ahead of print date: 21 June 2022

Published date: 21 June 2022

Additional Information: Funding Information: the authors would like to thank the core facilities that contributed to this work: the Research Histology at Department of Cellular Pathology, Southampton General Hospital for conducting histology and immunohistochemistry experiments; the Biomedical Imaging Unit at Southampton General Hospital for use of their bioimaging equipment and expertise, namely in fluorescent laser-scanning confocal microscopy and digital slide scanning. Gene expression data in Figure 1C ewers partly based on data generated by the TCGA Research Network: https://www.cancer.gov/tcga. The data used for the analyses described in this manuscript were obtained from the Genotype-Tissue Expression (GTEx) Project, which was supported by the Common Fund of the Office of the Director of the National Institutes of Health and by NCI, NHGRI, NHLBI, NIDA, NIMH, and NINDS. Funding: Medical Research Council UK Clinician Scientist Fellowship to T.J.U. “Exploring stromal-epithelial interactions in oesophageal cancer” G1002565 IDN0. 99762; Cancer Research UK & Royal College of Surgeons of England Advanced Clinician Scientist Fellowship to T.J.U. “Cellular interplay in oesophageal cancer.” A23924. A.H. performed experiments, interpreted results, conducted analysis, and wrote manuscript; A.M. performed experiments, interpreted results, and wrote manuscript; A.C. performed experiments, interpreted results, and wrote manuscript; R.W. performed experiments, interpreted results, and wrote manuscript; B.P.S. interpreted results, conducted analysis, and wrote manuscript; J.H. performed experiments; F.I. performed analysis and interpreted results; S.P.B. interpreted results and wrote manuscript; J.G. and O.P. performed analysis and interpreted results; E.J. contributed resources; E.K. performed experiments; J.H.S. S.P. A.A.R. P.A.C. N.P.M. D.O.B. K.Y-U,. and P.C. performed experiments, interpreted results, and wrote manuscript; S.D.G. performed experiments, interpreted results, and wrote manuscript; M.R.Z. performed experiments, interpreted results, and wrote manuscript; A.G. designed study, interpreted results, and wrote manuscript; T.J.U. raised funding, designed study, performed experiments, interpreted results, and wrote manuscript. All authors revised the manuscript and approved the final version. S.D.G. is Founder, President, CEO, and CTO of Proteas Bioanalytics, Inc. A.M. is CSO of Proteas Bioanalytics, Inc. They confirm that they were not affiliated when the work published in this study was carried out. All other authors declare no competing interests. One or more of the authors of this paper self-identifies as an underrepresented ethnic minority in science. One or more of the authors of this paper self-identifies as a member of the LGBTQ+ community. One or more of the authors of this paper self-identifies as living with a disability. Funding Information: the authors would like to thank the core facilities that contributed to this work: the Research Histology at Department of Cellular Pathology, Southampton General Hospital for conducting histology and immunohistochemistry experiments; the Biomedical Imaging Unit at Southampton General Hospital for use of their bioimaging equipment and expertise, namely in fluorescent laser-scanning confocal microscopy and digital slide scanning. Gene expression data in Figure 1 C ewers partly based on data generated by the TCGA Research Network: https://www.cancer.gov/tcga . The data used for the analyses described in this manuscript were obtained from the Genotype-Tissue Expression (GTEx) Project, which was supported by the Common Fund of the Office of the Director of the National Institutes of Health and by NCI, NHGRI, NHLBI, NIDA, NIMH, and NINDS. Funding: Medical Research Council UK Clinician Scientist Fellowship to T.J.U. “Exploring stromal-epithelial interactions in oesophageal cancer” G1002565 IDN0. 99762 ; Cancer Research UK & Royal College of Surgeons of England Advanced Clinician Scientist Fellowship to T.J.U. “Cellular interplay in oesophageal cancer.” A23924 .

Keywords: cancer-associated fibroblasts, chemotherapy, esophageal adenocarcinoma, phosphodiesterase type 5 inhibitors, preclinical models

Local EPrints ID: 468689

URI: http://eprints.soton.ac.uk/id/eprint/468689

DOI: doi:10.1016/j.xcrm.2022.100541

ISSN: 2666-3791

PURE UUID: 303599e6-c9b5-40fa-8374-d14b481a4749

ORCID for Jane Gibson: orcid.org/0000-0002-0973-8285

ORCID for Zoë Walters: orcid.org/0000-0002-1835-5868

ORCID for Matthew Rose-Zerilli: orcid.org/0000-0002-1064-5350

ORCID for Timothy J. Underwood: orcid.org/0000-0001-9455-2188

Date deposited: 22 Aug 2022 17:13

Last modified: 06 Jun 2024 02:00