Proteomic profile of melanoma cell‐derived small extracellular vesicles in patients’ plasma: a potential correlate of melanoma progression

Pietrowska, Monika; Zebrowska, Aneta; Gawin, Marta; Marczak, Łukasz; Mondal, Sujan Kumar; Mika, Justyna; Polańska, Joanna; Ferrone, Soldano; Kirkwood, John M.; Widłak, Piotr; Whiteside, Theresa L.

doi:10.1002/jev2.12063

Cited by 41 publications

(57 citation statements)

References 51 publications

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“…Besides, this molecule profile was also detected in biopsies of melanoma patients with a poor prognosis, thus representing a specific signature stage-disease related [ 66 ]. In line with this study, some of these proteins (GNS, CFL, HSP90AB1) were found upregulated in Exo derived from plasma of melanoma patients when compared to healthy donors [ 69 ]. These results suggest that acidic Mexo are carriers of specific molecules associated with the advanced stage of the disease, and therefore they can be considered a potential reservoirs of prognostic biomarkers.…”

Section: How Acidity and Hypoxia Modulate Melanoma Progression Through Mexosupporting

confidence: 70%

Acidic and Hypoxic Microenvironment in Melanoma: Impact of Tumour Exosomes on Disease Progression

Boussadia

Gambardella

Mattei

et al. 2021

Cells

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The mechanisms of melanoma progression have been extensively studied in the last decade, and despite the diagnostic and therapeutic advancements pursued, malignant melanoma still accounts for 60% of skin cancer deaths. Therefore, research efforts are required to better define the intercellular molecular steps underlying the melanoma development. In an attempt to represent the complexity of the tumour microenvironment (TME), here we analysed the studies on melanoma in acidic and hypoxic microenvironments and the interactions with stromal and immune cells. Within TME, acidity and hypoxia force melanoma cells to adapt and to evolve into a malignant phenotype, through the cooperation of the tumour-surrounding stromal cells and the escape from the immune surveillance. The role of tumour exosomes in the intercellular crosstalk has been generally addressed, but less studied in acidic and hypoxic conditions. Thus, this review aims to summarize the role of acidic and hypoxic microenvironment in melanoma biology, as well as the role played by melanoma-derived exosomes (Mexo) under these conditions. We also present a perspective on the characteristics of acidic and hypoxic exosomes to disclose molecules, to be further considered as promising biomarkers for an early detection of the disease. An update on the use of exosomes in melanoma diagnosis, prognosis and response to treatment will be also provided and discussed.

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Section: How Acidity and Hypoxia Modulate Melanoma Progression Through Mexosupporting

confidence: 70%

Acidic and Hypoxic Microenvironment in Melanoma: Impact of Tumour Exosomes on Disease Progression

Boussadia

Gambardella

Mattei

et al. 2021

Cells

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“…In recent years, exosomes have emerged as an important liquid biopsy tool for a variety of malignant tumors ( 24 ). With the development of mass spectrometry and other detection technologies, the protein composition of exosomes has been constantly identified; some of these are already used as tumor biomarkers due to their stability and specificity ( 20 , 25 ). Amongst them, Glycosyl-Phosphatidyl-Inositol (GPI) anchored proteins (GPI-APs) are attractive as a source of exosomal candidates ( 26 ).…”

Section: Discussionmentioning

confidence: 99%

“…(F) ROC curves analysis for the detection of PHCCA using exosomal Cripto-1 in both CA19-9 and CEA negative individuals. technologies, the protein composition of exosomes has been constantly identified; some of these are already used as tumor biomarkers due to their stability and specificity (20,25). Amongst them, Glycosyl-Phosphatidyl-Inositol (GPI) anchored proteins (GPI-APs) are attractive as a source of exosomal candidates (26).…”

Section: Discussionmentioning

confidence: 99%

Exosomal Cripto-1 Serves as a Potential Biomarker for Perihilar Cholangiocarcinoma

Zhang

et al. 2021

Front. Oncol.

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Perihilar cholangiocarcinoma (PHCCA) has a poor prognosis, mainly due to diagnosis at an advanced stage. Cripto-1 functions as an oncogene and is highly expressed in several human cancers, however, its clinical application in PHCCA is poorly understood. Herein, we identified that Cripto-1 was released by PHCCA cells via exosomes in vitro and in vivo. Furthermore, an ELISA method was developed to detect exosomal Cripto-1 in the serum of 115 PHCCA patients, 47 cholangitis patients and 65 healthy controls, and it was found that exosomal Cripto-1 was increased in PHCCA patients and associated with metastasis. Compared with traditional serum tumor markers, CA19-9 and CEA, exosomal Cripto-1 demonstrated a larger area under ROC curve for PHCCA diagnosis. The cutoff value of exosomal Cripto-1 was 0.82, achieving a sensitivity of 79.1% and a specificity of 87.5%. As expected, exosomal Cripto-1 levels in immunohistochemically Cripto-1-high cases were significantly elevated compared to in Cripto-1-low cases. When measured 1-week postoperatively, Cripto-1 levels decreased on average from 1.25(0.96-3.26) to 0.85(0.62-1.82). Immunohistochemistry analysis showed Cripto-1 expression was negatively correlated with E-cadherin and was an independent prognostic biomarker for poor survival in PHCCA patients. In conclusion, exosomal Cripto-1 in sera can reflect its expression in the tissue of PHCAA patients and has the potential be a non-invasive biomarker for diagnosis and prognosis of PHCCA.

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“…The presence of cancer may indeed influence the plasma EV population, as also recently found by Pietrowska et al, who captured melanoma and non-melanoma-derived EV in the plasma of 15 patients, comprising also stage I-II patients at diagnosis. According to their data, in plasma of these patients they could also capture melanoma antigen CSPG4, indicating the presence of melanoma-derived EV at the systemic level, despite the early stage of disease [61]. Thus, we are confident that our results-although gathered from a small cohort and not validated, a limitation of our study-may nonetheless advance the field, even if still far from translation into the clinical practice.…”

Section: Discussionmentioning

confidence: 69%

“…Notably, in this context, EV have generated enthusiasm due to their potential utility in liquid biopsies [59,60]. Plasma-derived EV from cancer patients could reflect in part the molecular and genetic contents of the releasing parent tumor cells, and thus their protein contents may be informative [61]. Similarly, lipid metabolic alterations of tumor cells have attracted major interest [62].…”

Section: Discussionmentioning

confidence: 99%

The Fatty Acid and Protein Profiles of Circulating CD81-Positive Small Extracellular Vesicles Are Associated with Disease Stage in Melanoma Patients

Paolino

Huber

Camerini³

et al. 2021

Cancers

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The early detection of cutaneous melanoma, a potentially lethal cancer with rising incidence, is fundamental to increasing survival and therapeutic adjustment. In stages II–IV especially, additional indications for adjuvant therapy purposes after resection and for treatment of metastatic patients are urgently needed. We investigated whether the fatty acid (FA) and protein compositions of small extracellular vesicles (sEV) derived from the plasma of stage 0–I, II and III–IV melanoma patients (n = 38) could reflect disease stage. The subpopulation of sEV expressing CD81 EV marker (CD81sEV) was captured by an ad hoc immune affinity technique from plasma depleted of large EV. Biological macromolecules were investigated by gas chromatography and mass spectrometry in CD81sEV. A higher content of FA was detectable in patients with respect to healthy donors (HD). Moreover, a higher C18:0/C18:1 ratio, as a marker of cell membrane fluidity, distinguished early (stage 0–I) from late (III–IV) stages’ CD81sEV. Proteomics detected increases in CD14, PON1, PON3 and APOA5 exclusively in stage II CD81sEV, and RAP1B was decreased in stage III–IV CD81sEV, in comparison to HD. Our results suggest that stage dependent alterations in CD81sEV’ FA and protein composition may occur early after disease onset, strengthening the potential of circulating sEV as a source of discriminatory information for early diagnosis, prediction of metastatic behavior and following up of melanoma patients.

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Proteomic profile of melanoma cell‐derived small extracellular vesicles in patients’ plasma: a potential correlate of melanoma progression

Cited by 41 publications

References 51 publications

Acidic and Hypoxic Microenvironment in Melanoma: Impact of Tumour Exosomes on Disease Progression

Acidic and Hypoxic Microenvironment in Melanoma: Impact of Tumour Exosomes on Disease Progression

Exosomal Cripto-1 Serves as a Potential Biomarker for Perihilar Cholangiocarcinoma

The Fatty Acid and Protein Profiles of Circulating CD81-Positive Small Extracellular Vesicles Are Associated with Disease Stage in Melanoma Patients

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