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

Autor: Aymeric Auger, Laura Santambrogio, Patricia Corthésy, Davide Demurtas, Emanuela Romano, Melody A. Swartz, Lambert Potin, Maurice Matter, Cristina C. Clement, Romain Hamelin, Alexandre Harari, Daniel E. Speiser, Natacha Bordry, Lea Maillat, Maria A. S. Broggi
Jazyk: angličtina
Rok vydání: 2019
Předmět:
0301 basic medicine
Proteomics
Skin Neoplasms
medicine.medical_treatment
pathways
Exosomes
Mice
0302 clinical medicine
Immunology and Allergy
Melanoma
Research Articles
S100 Proteins
Extracellular vesicle
Exudates and Transudates
proteomic analysis
invasion
macrophages
Lymphatic system
030220 oncology & carcinogenesis
Lymphatic Metastasis
Cytokines
Lymph
medicine.symptom
Exudate
Immunology
Article
03 medical and health sciences
Extracellular Vesicles
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 Vessels/metabolism
Melanoma/blood
Melanoma/pathology
Melanoma/secondary
Melanoma/surgery
Mice
Inbred C57BL
MicroRNAs/analysis
Proteomics/methods
S100 Proteins/analysis
Skin Neoplasms/blood
Skin Neoplasms/pathology
Skin Neoplasms/secondary
Skin Neoplasms/surgery
medicine
Biomarkers
Tumor
Lymphatic Vessels
business.industry
Cancer
medicine.disease
cancer progression
proteins
MicroRNAs
030104 developmental biology
Cancer research
peptides
cells
Lymphadenectomy
Cancer biomarkers
business
Zdroj: The Journal of Experimental Medicine
The Journal of experimental medicine, vol. 216, no. 5, pp. 1091-1107
ISSN: 1540-9538
0022-1007
Popis: Identifying cancer biomarkers is of great interest for patient prognosis and monitoring. However, tumor-associated factors are diluted in blood and challenging to detect. Broggi et al. show that lymphatic exudate, accessible at the time of lymphadenectomy, is highly enriched in tumor-associated factors and therefore a promising source for biomarker discovery.
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+ 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.
Graphical Abstract
Databáze: OpenAIRE
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