CD44v3 protein-carrying tumor-derived exosomes in HNSCC patients' plasma as potential noninvasive biomarkers of disease activity.

Abstract

The molecular cargo of tumor-cell-derived exosomes (TEX) mimics that of parental tumor cells. Thus, TEX could potentially serve as noninvasive biomarkers of cancer progression. However, separation of TEX from non-TEX in patients' plasma requires tumor antigen-specific detection reagents. CD44v3 has been of interest as a potential biomarker of disease progression in HNSCC, because its overexpression in tumor cells associates with poor outcome. Here, CD44v3+ TEX immunocaptured from plasma of 44 HNSCC patients and 7 healthy donors (HDs) were evaluated as potential biomarkers of disease activity and stage. Exosomes were isolated from plasma of by size exclusion chromatography. Using anti-CD44v3 or anti-CD3 mAbs on beads, CD44v3+ TEX CD3(-)TEX-enriched exosomes were immunocaptured from supernatants of nonmalignant or HNSCC cell lines and from patients' plasma. On-bead flow cytometry was used for the detection of FAS-L, PD-L1, TGFF-β. CSPG4 or EGFR on exosomes. The TEX expression profiles were correlated to clinicopathological parameters. Relative florescence intensity (RFI) values for CD44v3 were higher (p < .01) on TEX from HNSCC cell lines or on CD44v3+ CD3(-) plasma-derived exosomes. RFI values of CD44v3 on CD3(-) exosomes were higher (p < .005) in patients than in HDs and correlated (p < .05) with the UICC stage and lymph node metastasis. In HNSCC patients, CD44v3+ exosomes higher levels of immunosuppressive proteins compared to CD44v3(-) exosomes (p < .05-p < .005), and RFI values for these markers correlated with higher disease stages and lymph node metastasis. Isolation of CD44v3+ exosomes by immunocapture allowed for enrichment of TEX which are potentially promising liquid biomarkers of the tumor burden and disease stage in HNSCC.

• Authors: Marie-Nicole Theodoraki, Akihiro Matsumoto, Inga Beccard, Thomas K Hoffmann, Theresa L Whiteside
• Journal: Oncoimmunology (Oncoimmunology) Vol. 9 Issue 1 Pg. 1747732 ( 2020) ISSN: 2162-4011 [Print] United States
• PMID: 32313730 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
• Copyright: © 2020 The Author(s). Published with license by Taylor & Francis Group, LLC.

Chemical References

• Biomarkers, Tumor
• CD44 protein, human
• Hyaluronan Receptors

Topics

• Adult
• Aged
• Aged, 80 and over
• Biomarkers, Tumor (blood)
• Exosomes
• Female
• Head and Neck Neoplasms (blood)
• Humans
• Hyaluronan Receptors (blood)
• Male
• Middle Aged
• Squamous Cell Carcinoma of Head and Neck (blood)