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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Autores principales:	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
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282
Acceso en línea:	https://doaj.org/article/faec4d711cb34b769d96bb88a3e5b5c2
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spelling	oai:doaj.org-article:faec4d711cb34b769d96bb88a3e5b5c22021-12-02T13:15:04ZProteomics of REPLICANT perfusate detects changes in the metastatic lymph node microenvironment10.1038/s41523-021-00227-72374-4677https://doaj.org/article/faec4d711cb34b769d96bb88a3e5b5c22021-03-01T00:00:00Zhttps://doi.org/10.1038/s41523-021-00227-7https://doaj.org/toc/2374-4677Abstract 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.Julia StevensonRachel Barrow-McGeeLu YuAngela PaulDavid MansfieldJulie OwenNatalie WoodmanRachael NatrajanSyed HaiderCheryl GillettAndrew TuttSarah E. PinderJyoti ChoudaryKalnisha NaidooNature PortfolioarticleNeoplasms. Tumors. Oncology. Including cancer and carcinogensRC254-282ENnpj Breast Cancer, Vol 7, Iss 1, Pp 1-13 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282
spellingShingle	Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282 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
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.
format	article
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
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 Portfolio
publishDate	2021
url	https://doaj.org/article/faec4d711cb34b769d96bb88a3e5b5c2
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Proteomics of REPLICANT perfusate detects changes in the metastatic lymph node microenvironment

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