High Levels of Exosomes Expressing CD63 and Caveolin-1 in Plasma of Melanoma Patients

By M. Logozzi, A. De Milito, L. Lugini, M. Borghi, L. Calabrò, M. Spada, M. Perdicchio, M. Marino, C. Federici, Elisabetta Iessi and 8 more. PLoS ONE, 2009

912 citations recorded by the source corpus.

Background Metastatic melanoma is an untreatable cancer lacking reliable and non-invasive markers of disease progression. Exosomes are small vesicles secreted by normal as well as tumor cells. Human tumor-derived exosomes are involved in malignant progression and we evaluated the presence of exosomes in plasma of melanoma patients as a potential tool for cancer screening and follow-up. Methodology/Principal Findings We designed an in-house sandwich ELISA (Exotest) to capture and quantify exosomes in plasma based on expression of housekeeping proteins (CD63 and Rab-5b) and a tumor-associated marker (caveolin-1). Western blot and flow cytometry analysis of exosomes were used to confirm the Exotest-based findings. The Exotest allowed sensitive detection and quantification of exosomes purified from human tumor cell culture supernatants and plasma from SCID mice engrafted with human melanoma. Plasma levels of exosomes in melanoma-engrafted SCID mice correlated to tumor size. We evaluated the levels of plasma exosomes expressing CD63 and caveolin-1 in melanoma patients (n = 90) and healthy donors (n = 58). Consistently, plasma exosomes expressing CD63 (504±315) or caveolin-1 (619±310) were significantly increased in melanoma patients as compared to healthy donors (223±125 and 228±102, respectively). While the Exotest for CD63+ plasma exosomes had limited sensitivity (43%) the Exotest for detection of caveolin-1+ plasma exosomes showed a higher sensitivity (68%). Moreover, caveolin-1+ plasma exosomes were significantly increased with respect to CD63+ exosomes in the patients group. Conclusions/Significance We describe a new non-invasive assay allowing detection and quantification of human exosomes in plasma of melanoma patients. Our results suggest that the Exotest for detection of plasma exosomes carrying tumor-associated antigens may represent a novel tool for clinical management of cancer patients.

View Paper: https://www.semanticscholar.org/paper/08ea80f94944c98e982ad87abcb01470906b4048

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Citations in the corpus

Exosomes reflect the hypoxic status of glioma cells and mediate hypoxia-dependent activation of vascular cells during tumor development (2013, background): “Further, CAV1 was shown to be hypoxia regulated and to be present in plasma exosomes of melanoma patients (28, 29).”
Routes and mechanisms of extracellular vesicle uptake (2014, background): “EVs, which are released in greater numbers by cancer cells (134), can promote tumour development and are involved in mediating intercellular communication within the tumour microenvironment (135).”
Cancer Exosomes Perform Cell-Independent MicroRNA Biogenesis and Promote Tumorigenesis. (2025, unknown): “Exosomes levels in the serum of breast cancer patients are generally higher when compared to normal subjects (Logozzi et al., 2009; Taylor and Gercel-Taylor, 2008; O'Brien et al., 2013). miRNAs are small noncoding RNAs of 18–24 nucleotides (nt) in length that control gene expression…”
Characterisation of exosomes derived from human cells by nanoparticle tracking analysis and scanning electron microscopy. (2011, background): “in melanoma [7] or in ovarian cancer diagnostics [8].”
Extracellular vesicles in cancer: cell-to-cell mediators of metastasis (2016, background): “Furthermore, exosomes from plasma of melanoma patients are enriched in caveolin-1 compared to the healthy controls, rendering caveolin-1 positive exosomes as another potential melanoma biomarker (Logozzi et al., 2009).”
Review of the Isolation, Characterization, Biological Function, and Multifarious Therapeutic Approaches of Exosomes (2019, background): “Furthermore, elevated levels of CD81 are associated with inflammation and the severity of fibrosis, indicating that CD81 may be a potential biomarker for hepatitis C diagnosis and treatment response [199,200].”
Body fluid derived exosomes as a novel template for clinical diagnostics (2011, background): “Indeed, exosomes can be isolated from various body fluids such as breast milk, serum, plasma, malignant ascites, and urine [9,13-17].”
Liquid biopsy: a step closer to transform diagnosis, prognosis and future of cancer treatments (2022, background): “Melanoma, PCa –– –– CD63 and caveolin‐1 [52, 53]”