Exosomes Released by Melanoma Cells Prepare Sentinel Lymph Nodes for Tumor Metastasis

TLDR

Exosomes are tumor‑derived nanovesicles that communicate signals, and melanoma exosomes trigger pro‑angiogenic remodeling of tissue matrices. This study demonstrates that melanoma exosomes condition sentinel lymph nodes and defines the microanatomic changes that enable metastatic colonization. Melanoma exosomes home to sentinel lymph nodes, delivering synchronized signals that recruit tumor cells, deposit extracellular matrix, and stimulate vascular proliferation. The results reveal that exosome‑mediated niche preparation in lymph nodes drives lymphatic metastasis of melanoma cells.

Abstract

Exosomes are naturally occurring biological nanovesicles utilized by tumors to communicate signals to local and remote cells and tissues. Melanoma exosomes can incite a proangiogenic signaling program capable of remodeling tissue matrices. In this study, we show exosome-mediated conditioning of lymph nodes and define microanatomic responses that license metastasis of melanoma cells. Homing of melanoma exosomes to sentinel lymph nodes imposes synchronized molecular signals that effect melanoma cell recruitment, extracellular matrix deposition, and vascular proliferation in the lymph nodes. Our findings highlight the pathophysiologic role and mechanisms of an exosome-mediated process of microanatomic niche preparation that facilitates lymphatic metastasis by cancer cells.