Diagnostic utility and functional analysis of exosomes from different stages of Head and Neck Cancer (HNC)

• Applicants: Professorin Dr. Jadwiga Jablonska-Koch; Privatdozentin Dr. Sonja Ludwig; Privatdozent Dr. Basant Kumar Thakur, Ph.D.
• Subject Area: Otolaryngology, Phoniatrics and Audiology
• Term: from 2018 to 2023
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 407063783

Late tumor recognition at advanced stages make Head and Neck Cancer (HNC) one of the deadliest malignant diseases worldwide. Exosomes, nanoparticles ranging from 30-120 nm in size and resembling their parent cells’ cargo, provide great potential to improve early tumor detection. As they suppress anti-tumor immune responses, their contribution to disease progression and metastasis is critical but in detail still widely unclear.In this study we aim to introduce exosomes as biomarkers in HNC by identifying their protein and double-stranded DNA cargo in cell culture, mouse and patient plasma. Following exosome isolation from these sources using a well-established size exclusion chromatography approach, we will conduct basic exosome characterization including electron microscopy, BCA protein assay, and size and concentration determination by ZetaView. To define immunoregulatory pathways we will utilize proteomics and Western blots and Next Generation Sequencing (NGS) to identify dsDNAs. Furthermore, we intend to examine the role of exosomes in mice and humans in promoting neutrophil-dependent pro-metastatic pathways. Therefore, we will isolate exosomes from HNC patients at various stages co-incubated with normal human neutrophils to identify the functional impact on regulatory pathways, migratory potential and cytotoxicity towards tumor cells. In mouse model oropharyngeal carcinoma cells and PKH-labeled exosomes will be injected to induce metastasis in tumor-bearing mice to unravel the involvement of exosomes in tumor progression, relapse and metastasis. Overall, the characteristics of exosomes in being small copies of their parent cells and their involvement in disease manifestation and progression could not only improve early tumor detection as a sort of liquid biopsies but also allow for novel, more powerful targeted therapies.

• DFG Programme: Research Grants