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)...
Saved in:
| Main Authors: | , , , , , , , , , , , , , |
|---|---|
| Format: | article |
| Language: | EN |
| Published: |
Nature Portfolio
2021
|
| Subjects: | |
| Online Access: | https://doaj.org/article/faec4d711cb34b769d96bb88a3e5b5c2 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| Summary: | 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. |
|---|