Tumor-associated factors are enriched in lymphatic exudate compared to plasma in metastatic melanoma patients.

Details

Serval ID
serval:BIB_83C31BFEAA5C
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Tumor-associated factors are enriched in lymphatic exudate compared to plasma in metastatic melanoma patients.
Journal
The Journal of experimental medicine
Author(s)
Broggi MAS, Maillat L., Clement C.C., Bordry N., Corthésy P., Auger A., Matter M., Hamelin R., Potin L., Demurtas D., Romano E., Harari A., Speiser D.E., Santambrogio L., Swartz M.A.
ISSN
1540-9538 (Electronic)
ISSN-L
0022-1007
Publication state
Published
Issued date
06/05/2019
Peer-reviewed
Oui
Volume
216
Number
5
Pages
1091-1107
Language
english
Notes
Publication types: Journal Article ; Research Support, Non-U.S. Gov't
Publication Status: ppublish
Abstract
Liquid biopsies allow monitoring of cancer progression and detection of relapse, but reliable biomarkers in melanoma are lacking. Because secreted factors preferentially drain to lymphatic vessels before dilution in the blood, we hypothesized that lymph should be vastly enriched in cancer biomarkers. We characterized postoperative lymphatic exudate and plasma of metastatic melanoma patients after lymphadenectomy and found a dramatic enrichment in lymphatic exudate of tumor-derived factors and especially extracellular vesicles containing melanoma-associated proteins and miRNAs, with unique protein signatures reflecting early versus advanced metastatic spread. Furthermore, lymphatic exudate was enriched in memory T cells, including tumor-reactive CD137 <sup>+</sup> and stem cell-like types. In mice, lymph vessels were the major route of extracellular vesicle transport from tumors to the systemic circulation. We suggest that lymphatic exudate provides a rich source of tumor-derived factors for enabling the discovery of novel biomarkers that may reflect disease stage and therapeutic response.
Keywords
Animals, Biomarkers, Tumor/analysis, Cell Line, Tumor, Cytokines/analysis, Exosomes/metabolism, Extracellular Vesicles/metabolism, Exudates and Transudates/metabolism, Humans, Lymph/metabolism, Lymph Node Excision, Lymphatic Metastasis, Lymphatic Vessels/metabolism, Melanoma/blood, Melanoma/pathology, Melanoma/secondary, Melanoma/surgery, Mice, Mice, Inbred C57BL, MicroRNAs/analysis, Proteomics/methods, S100 Proteins/analysis, Skin Neoplasms/blood, Skin Neoplasms/pathology, Skin Neoplasms/secondary, Skin Neoplasms/surgery
Pubmed
Web of science
Open Access
Yes
Create date
28/04/2019 16:33
Last modification date
23/06/2020 6:21
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