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Fibroblast Activation Protein Specific Optical Imaging in Non-Small Cell Lung Cancer

Fibroblast activation protein (FAP) is a cell surface propyl-specific serine protease involved in the regulation of extracellular matrix. Whilst expressed at low levels in healthy tissue, upregulation of FAP on fibroblasts can be found in several solid organ malignancies, including non-small cell lu...

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Autores principales: Mathieson, Layla, O’Connor, Richard A., Stewart, Hazel, Shaw, Paige, Dhaliwal, Kevin, Williams, Gareth O. S., Megia-Fernandez, Alicia, Akram, Ahsan R.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8961646/
https://www.ncbi.nlm.nih.gov/pubmed/35359378
http://dx.doi.org/10.3389/fonc.2022.834350
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author Mathieson, Layla
O’Connor, Richard A.
Stewart, Hazel
Shaw, Paige
Dhaliwal, Kevin
Williams, Gareth O. S.
Megia-Fernandez, Alicia
Akram, Ahsan R.
author_facet Mathieson, Layla
O’Connor, Richard A.
Stewart, Hazel
Shaw, Paige
Dhaliwal, Kevin
Williams, Gareth O. S.
Megia-Fernandez, Alicia
Akram, Ahsan R.
author_sort Mathieson, Layla
collection PubMed
description Fibroblast activation protein (FAP) is a cell surface propyl-specific serine protease involved in the regulation of extracellular matrix. Whilst expressed at low levels in healthy tissue, upregulation of FAP on fibroblasts can be found in several solid organ malignancies, including non-small cell lung cancer, and chronic inflammatory conditions such as pulmonary fibrosis and rheumatoid arthritis. Their full role remains unclear, but FAP expressing cancer associated fibroblasts (CAFs) have been found to relate to a poor prognosis with worse survival rates in breast, colorectal, pancreatic, and non-small cell lung cancer (NSCLC). Optical imaging using a FAP specific chemical probe, when combined with clinically compatible imaging systems, can provide a readout of FAP activity which could allow disease monitoring, prognostication and potentially stratify therapy. However, to derive a specific signal for FAP any sequence must retain specificity over closely related endopeptidases, such as prolyl endopeptidase (PREP), and be resistant to degradation in areas of active inflammation. We describe the iterative development of a FAP optical reporter sequence which retains FAP specificity, confers resistance to degradation in the presence of activated neutrophil proteases and demonstrates clinical tractability ex vivo in NSCLC samples with an imaging platform.
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spelling pubmed-89616462022-03-30 Fibroblast Activation Protein Specific Optical Imaging in Non-Small Cell Lung Cancer Mathieson, Layla O’Connor, Richard A. Stewart, Hazel Shaw, Paige Dhaliwal, Kevin Williams, Gareth O. S. Megia-Fernandez, Alicia Akram, Ahsan R. Front Oncol Oncology Fibroblast activation protein (FAP) is a cell surface propyl-specific serine protease involved in the regulation of extracellular matrix. Whilst expressed at low levels in healthy tissue, upregulation of FAP on fibroblasts can be found in several solid organ malignancies, including non-small cell lung cancer, and chronic inflammatory conditions such as pulmonary fibrosis and rheumatoid arthritis. Their full role remains unclear, but FAP expressing cancer associated fibroblasts (CAFs) have been found to relate to a poor prognosis with worse survival rates in breast, colorectal, pancreatic, and non-small cell lung cancer (NSCLC). Optical imaging using a FAP specific chemical probe, when combined with clinically compatible imaging systems, can provide a readout of FAP activity which could allow disease monitoring, prognostication and potentially stratify therapy. However, to derive a specific signal for FAP any sequence must retain specificity over closely related endopeptidases, such as prolyl endopeptidase (PREP), and be resistant to degradation in areas of active inflammation. We describe the iterative development of a FAP optical reporter sequence which retains FAP specificity, confers resistance to degradation in the presence of activated neutrophil proteases and demonstrates clinical tractability ex vivo in NSCLC samples with an imaging platform. Frontiers Media S.A. 2022-03-10 /pmc/articles/PMC8961646/ /pubmed/35359378 http://dx.doi.org/10.3389/fonc.2022.834350 Text en Copyright © 2022 Mathieson, O’Connor, Stewart, Shaw, Dhaliwal, Williams, Megia-Fernandez and Akram https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Oncology
Mathieson, Layla
O’Connor, Richard A.
Stewart, Hazel
Shaw, Paige
Dhaliwal, Kevin
Williams, Gareth O. S.
Megia-Fernandez, Alicia
Akram, Ahsan R.
Fibroblast Activation Protein Specific Optical Imaging in Non-Small Cell Lung Cancer
title Fibroblast Activation Protein Specific Optical Imaging in Non-Small Cell Lung Cancer
title_full Fibroblast Activation Protein Specific Optical Imaging in Non-Small Cell Lung Cancer
title_fullStr Fibroblast Activation Protein Specific Optical Imaging in Non-Small Cell Lung Cancer
title_full_unstemmed Fibroblast Activation Protein Specific Optical Imaging in Non-Small Cell Lung Cancer
title_short Fibroblast Activation Protein Specific Optical Imaging in Non-Small Cell Lung Cancer
title_sort fibroblast activation protein specific optical imaging in non-small cell lung cancer
topic Oncology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8961646/
https://www.ncbi.nlm.nih.gov/pubmed/35359378
http://dx.doi.org/10.3389/fonc.2022.834350
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