Charakterisierung von EZH2 als therapeutisches Target des Olfaktoriusneuroblastoms

Introduction: Olfactory neuroblastoma (ONB) is a rare tumor of the nasal cavity, originating from stem cells of the olfactory epithelium. Recently, our research group demonstrated that the pharmacologic target EZH2 is highly expressed in the proliferating ONB cells, potentially serving as a promising target for pharmacological therapy. However, to date, no immortalized cell line has been established for ONB, and only three primary cell cultures have been described in the literature, limiting preclinical studies such as the pharmacological inhibition of EZH2.
Material/Methods: Primary ONB samples were mechanically and enzymatically dissociated, then snap-frozen or immediately seeded onto coated culture plates in cell culture medium supplemented with FBS. Immunostaining and single-cell sequencing were performed according to established protocols.
Results: We successfully established the first three-dimensional organoid culture of ONB, which expresses EZH2 along with other markers commonly used in histopathological diagnostics, such as NeuroD1 and PGP9.5. Interestingly, the cultivation of ONB organoids relies on co-culture with autologous cancer-associated fibroblasts (CAFs), which exhibit strong expression of CDH11, POSTN, and genes associated with collagen production, adhesion, and migration, closely resembling the phenotype of matrix-associated CAFs.
Conclusion: Our organoid models provide a validated ex vivo model of ONB for pharmacological testing. In a prospective, DFG-funded study (#549202461), we are evaluating the effect of EZH2 inhibition, such as with Tazemetostat, an FDA-approved small molecule already used in clinical practice. We anticipate that the results will offer insights into personalized tumor therapy for ONB, particularly for non-resectable cases.

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