Proteomics of REPLICANT perfusate detects changes in the metastatic lymph node microenvironment.
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Embargo End Date
ICR Authors
Authors
Stevenson, J
Barrow-McGee, R
Yu, L
Paul, A
Mansfield, D
Owen, J
Woodman, N
Natrajan, R
Haider, S
Gillett, C
Tutt, A
Pinder, SE
Choudary, J
Naidoo, K
Barrow-McGee, R
Yu, L
Paul, A
Mansfield, D
Owen, J
Woodman, N
Natrajan, R
Haider, S
Gillett, C
Tutt, A
Pinder, SE
Choudary, J
Naidoo, K
Document Type
Journal Article
Date
2021-03-05
Date Accepted
2021-01-20
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.
Citation
NPJ breast cancer, 2021, 7 (1), pp. 24 - ?
Source Title
Publisher
NATURE PORTFOLIO
ISSN
2374-4677
eISSN
2374-4677
Collections
Research Team
Functional Genomics
Functional Genomics
Functional Genomics