Proteomics of REPLICANT perfusate detects changes in the metastatic lymph node microenvironment
Abstract In breast cancer (BC), detecting low volumes of axillary lymph node (ALN) metastasis pre-operatively is difficult and novel biomarkers are needed. We recently showed that patient-derived ALNs can be sustained ex-vivo using normothermic perfusion. We now compare reactive (tumour-free; n = 5)...
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2021-03-01
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Series: | npj Breast Cancer |
Online Access: | https://doi.org/10.1038/s41523-021-00227-7 |
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doaj-faec4d711cb34b769d96bb88a3e5b5c22021-03-11T11:14:25ZengNature Publishing Groupnpj Breast Cancer2374-46772021-03-017111310.1038/s41523-021-00227-7Proteomics of REPLICANT perfusate detects changes in the metastatic lymph node microenvironmentJulia Stevenson0Rachel Barrow-McGee1Lu Yu2Angela Paul3David Mansfield4Julie Owen5Natalie Woodman6Rachael Natrajan7Syed Haider8Cheryl Gillett9Andrew Tutt10Sarah E. Pinder11Jyoti Choudary12Kalnisha Naidoo13The Breast Cancer Now Toby Robins Research Centre, The Institute of Cancer ResearchThe Breast Cancer Now Toby Robins Research Centre, The Institute of Cancer ResearchDivision of Cancer Biology, The Institute of Cancer ResearchDivision of Cancer Biology, The Institute of Cancer ResearchDivision of Radiotherapy and Imaging, The Institute of Cancer ResearchKing’s Health Partners Cancer Biobank, Guy’s Comprehensive Cancer CentreKing’s Health Partners Cancer Biobank, Guy’s Comprehensive Cancer CentreThe Breast Cancer Now Toby Robins Research Centre, The Institute of Cancer ResearchThe Breast Cancer Now Toby Robins Research Centre, The Institute of Cancer ResearchKing’s Health Partners Cancer Biobank, Guy’s Comprehensive Cancer CentreThe Breast Cancer Now Toby Robins Research Centre, The Institute of Cancer ResearchSchool of Cancer and Pharmaceutical Sciences, King’s College London, Guy’s Comprehensive Cancer CentreDivision of Cancer Biology, The Institute of Cancer ResearchThe Breast Cancer Now Toby Robins Research Centre, The Institute of Cancer ResearchAbstract In breast cancer (BC), detecting low volumes of axillary lymph node (ALN) metastasis pre-operatively is difficult and novel biomarkers are needed. We recently showed that patient-derived ALNs can be sustained ex-vivo using normothermic perfusion. We now compare reactive (tumour-free; n = 5) and macrometastatic (containing tumour deposits >2 mm; n = 4) ALNs by combining whole section multiplex immunofluorescence with TMT-labelled LC-MS/MS of the circulating perfusate. Macrometastases contained significantly fewer B cells and T cells (CD4+/CD8+/regulatory) than reactive nodes (p = 0.02). Similarly, pathway analysis of the perfusate proteome (119/1453 proteins significantly differentially expressed) showed that immune function was diminished in macrometastases in favour of ‘extracellular matrix degradation’; only ‘neutrophil degranulation’ was preserved. Qualitative comparison of the perfusate proteome to that of node-positive pancreatic and prostatic adenocarcinoma also highlighted ‘neutrophil degranulation’ as a contributing factor to nodal metastasis. Thus, metastasis-induced changes in the REPLICANT perfusate proteome are detectable, and could facilitate biomarker discovery.https://doi.org/10.1038/s41523-021-00227-7 |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Julia Stevenson Rachel Barrow-McGee Lu Yu Angela Paul David Mansfield Julie Owen Natalie Woodman Rachael Natrajan Syed Haider Cheryl Gillett Andrew Tutt Sarah E. Pinder Jyoti Choudary Kalnisha Naidoo |
spellingShingle |
Julia Stevenson Rachel Barrow-McGee Lu Yu Angela Paul David Mansfield Julie Owen Natalie Woodman Rachael Natrajan Syed Haider Cheryl Gillett Andrew Tutt Sarah E. Pinder Jyoti Choudary Kalnisha Naidoo Proteomics of REPLICANT perfusate detects changes in the metastatic lymph node microenvironment npj Breast Cancer |
author_facet |
Julia Stevenson Rachel Barrow-McGee Lu Yu Angela Paul David Mansfield Julie Owen Natalie Woodman Rachael Natrajan Syed Haider Cheryl Gillett Andrew Tutt Sarah E. Pinder Jyoti Choudary Kalnisha Naidoo |
author_sort |
Julia Stevenson |
title |
Proteomics of REPLICANT perfusate detects changes in the metastatic lymph node microenvironment |
title_short |
Proteomics of REPLICANT perfusate detects changes in the metastatic lymph node microenvironment |
title_full |
Proteomics of REPLICANT perfusate detects changes in the metastatic lymph node microenvironment |
title_fullStr |
Proteomics of REPLICANT perfusate detects changes in the metastatic lymph node microenvironment |
title_full_unstemmed |
Proteomics of REPLICANT perfusate detects changes in the metastatic lymph node microenvironment |
title_sort |
proteomics of replicant perfusate detects changes in the metastatic lymph node microenvironment |
publisher |
Nature Publishing Group |
series |
npj Breast Cancer |
issn |
2374-4677 |
publishDate |
2021-03-01 |
description |
Abstract In breast cancer (BC), detecting low volumes of axillary lymph node (ALN) metastasis pre-operatively is difficult and novel biomarkers are needed. We recently showed that patient-derived ALNs can be sustained ex-vivo using normothermic perfusion. We now compare reactive (tumour-free; n = 5) and macrometastatic (containing tumour deposits >2 mm; n = 4) ALNs by combining whole section multiplex immunofluorescence with TMT-labelled LC-MS/MS of the circulating perfusate. Macrometastases contained significantly fewer B cells and T cells (CD4+/CD8+/regulatory) than reactive nodes (p = 0.02). Similarly, pathway analysis of the perfusate proteome (119/1453 proteins significantly differentially expressed) showed that immune function was diminished in macrometastases in favour of ‘extracellular matrix degradation’; only ‘neutrophil degranulation’ was preserved. Qualitative comparison of the perfusate proteome to that of node-positive pancreatic and prostatic adenocarcinoma also highlighted ‘neutrophil degranulation’ as a contributing factor to nodal metastasis. Thus, metastasis-induced changes in the REPLICANT perfusate proteome are detectable, and could facilitate biomarker discovery. |
url |
https://doi.org/10.1038/s41523-021-00227-7 |
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