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.