Plasma exosomes identify metastatic potential in early stage melanoma

Exosomes are emerging as key players in cancer progression, facilitating local and distant interactions that contribute to tumor metastasis. Survival with malignant melanoma rapidly decreases following metastatic spread. Patients with a diagnosis of metastatic melanoma experience a five-year survival rate which decreases from 91.3% (no metastasis) to 16%. It is imperative that early detection of metastatic melanoma is implemented to improve survival rates. Known as “messengers of metastasis”, exosomes provide a reflection of their cell of origin, unveiling critical insights into tumor microenvironment maintenance and metastatic behavior. Using stage I patient samples with metastatic melanoma as well as a mouse model, we isolated exosomes from the local environment, such as the primary tumor, as well as through the bloodstream. From nanoparticle analysis, exosome concentration differed within the localized and systemic environments among stage I patients, further supporting our understanding of the heterogeneity among patient tumors, despite being classified in the same stage of cancer. Proteomic analysis of exosomes with mass spectrometry conveyed stark differences in the expression of proteins found in the localized, tumor environment and those found in the systemic environment of which plasma-derived exosomes were isolated. Eighteen proteins with known metastatic characteristics were statistically found to be uniquely expressed in the bloodstream or in the primary tumor. Interestingly, plasma-derived exosomes containing metastatic proteins were found in the patients with stage I melanoma. These proteins may serve as an early indicator of metastatic melanoma with further studies.