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Article

Increased Tenascin C, Osteopontin and HSP90 Levels in Plasmatic Small Extracellular Vesicles of Pediatric ALK-Positive Anaplastic Large Cell Lymphoma: New Prognostic Biomarkers?

by
Federica Lovisa
1,2,†,
Anna Garbin
1,2,†,
Sara Crotti
2,
Piero Di Battista
1,2,
Ilaria Gallingani
1,2,
Carlotta Caterina Damanti
1,2,
Anna Tosato
1,2,
Elisa Carraro
3,
Marta Pillon
3,
Erfan Mafakheri
4,
Filippo Romanato
4,5,
Enrico Gaffo
6,
Alessandra Biffi
1,2,
Stefania Bortoluzzi
6,7,
Marco Agostini
2,8 and
Lara Mussolin
1,2,*
1
Maternal and Child Health Department, Padova University, 35128 Padova, Italy
2
Istituto di Ricerca Pediatrica Città della Speranza, 35127 Padova, Italy
3
Pediatric Hematology, Oncology and Stem Cell Transplant Division, Padova University Hospital, 35128 Padova, Italy
4
Department of Physics and Astronomy, Padova University, 35131 Padova, Italy
5
IOM-CNR, S.S. 14 km 163,5, 34149 Trieste, Italy
6
Department of Molecular Medicine, Padova University, 35121 Padova, Italy
7
CRIBI Interdepartmental Research Center for Innovative Biotechnologies (CRIBI), Padova University, 35121 Padova, Italy
8
First Surgical Clinic Section, Department of Surgical, Oncological and Gastroenterological Sciences, Padova University, 35128 Padova, Italy
*
Author to whom correspondence should be addressed.
†
These authors contributed equally.
Diagnostics 2021, 11(2), 253; https://doi.org/10.3390/diagnostics11020253
Submission received: 24 November 2020 / Revised: 1 February 2021 / Accepted: 2 February 2021 / Published: 6 February 2021
(This article belongs to the Special Issue Diagnostic Potential of Extracellular Vesicles (EVs) in Chronic Diseases)
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Abstract

Over the past 15 years, several biological and pathological characteristics proved their significance in pediatric anaplastic lymphoma kinase (ALK)-positive anaplastic large-cell lymphoma (ALCL) prognostic stratification. However, the identification of new non-invasive disease biomarkers, relying on the most important disease mechanisms, is still necessary. In recent years, plasmatic circulating small extracellular vesicles (S-EVs) gathered great importance both as stable biomarker carriers and active players in tumorigenesis. In the present work, we performed a comprehensive study on the proteomic composition of plasmatic S-EVs of pediatric ALCL patients compared to healthy donors (HDs). By using a mass spectrometry-based proteomics approach, we identified 50 proteins significantly overrepresented in S-EVs of ALCL patients. Gene Ontology enrichment analysis disclosed cellular components and molecular functions connected with S-EV origin and vesicular trafficking, whereas cell adhesion, glycosaminoglycan metabolic process, extracellular matrix organization, collagen fibril organization and acute phase response were the most enriched biological processes. Of importance, consistently with the presence of nucleophosmin (NPM)-ALK fusion protein in ALCL cells, a topological enrichment analysis based on Reactome- and Kyoto Encyclopedia of Genes and Genomes (KEGG)-derived networks highlighted a dramatic increase in proteins of the phosphatidylinositol 3-kinase (PI3K)/AKT pathway in ALCL S-EVs, which included heat shock protein 90-kDa isoform alpha 1 (HSP90AA1), osteopontin (SPP1/OPN) and tenascin C (TNC). These results were validated by Western blotting analysis on a panel of ALCL and HD cases. Further research is warranted to better define the role of these S-EV proteins as diagnostic and, possibly, prognostic parameters at diagnosis and for ALCL disease monitoring.
Keywords: ALCL; small EVs; proteomics; osteopontin; tenascin C; HSP90 ALCL; small EVs; proteomics; osteopontin; tenascin C; HSP90

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MDPI and ACS Style

Lovisa, F.; Garbin, A.; Crotti, S.; Di Battista, P.; Gallingani, I.; Damanti, C.C.; Tosato, A.; Carraro, E.; Pillon, M.; Mafakheri, E.; et al. Increased Tenascin C, Osteopontin and HSP90 Levels in Plasmatic Small Extracellular Vesicles of Pediatric ALK-Positive Anaplastic Large Cell Lymphoma: New Prognostic Biomarkers? Diagnostics 2021, 11, 253. https://doi.org/10.3390/diagnostics11020253

AMA Style

Lovisa F, Garbin A, Crotti S, Di Battista P, Gallingani I, Damanti CC, Tosato A, Carraro E, Pillon M, Mafakheri E, et al. Increased Tenascin C, Osteopontin and HSP90 Levels in Plasmatic Small Extracellular Vesicles of Pediatric ALK-Positive Anaplastic Large Cell Lymphoma: New Prognostic Biomarkers? Diagnostics. 2021; 11(2):253. https://doi.org/10.3390/diagnostics11020253

Chicago/Turabian Style

Lovisa, Federica, Anna Garbin, Sara Crotti, Piero Di Battista, Ilaria Gallingani, Carlotta Caterina Damanti, Anna Tosato, Elisa Carraro, Marta Pillon, Erfan Mafakheri, and et al. 2021. "Increased Tenascin C, Osteopontin and HSP90 Levels in Plasmatic Small Extracellular Vesicles of Pediatric ALK-Positive Anaplastic Large Cell Lymphoma: New Prognostic Biomarkers?" Diagnostics 11, no. 2: 253. https://doi.org/10.3390/diagnostics11020253

APA Style

Lovisa, F., Garbin, A., Crotti, S., Di Battista, P., Gallingani, I., Damanti, C. C., Tosato, A., Carraro, E., Pillon, M., Mafakheri, E., Romanato, F., Gaffo, E., Biffi, A., Bortoluzzi, S., Agostini, M., & Mussolin, L. (2021). Increased Tenascin C, Osteopontin and HSP90 Levels in Plasmatic Small Extracellular Vesicles of Pediatric ALK-Positive Anaplastic Large Cell Lymphoma: New Prognostic Biomarkers? Diagnostics, 11(2), 253. https://doi.org/10.3390/diagnostics11020253

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