HPV-positive head and neck squamous cell carcinoma cells lose viability during triggered myocyte lineage differentiation

Gendreizig, S.; Martinez-Ruiz, L.; Lopez-Rodriguez, A.; Pabla, H.; Hose, L.; Brasch, F.; Busche, T.; Escames, G.; Sudhoff, H.; Scholtz, L. U.; Todt, I.; Oppel, F.

doi:10.1101/2024.03.28.587125

bioRxiv · 10.1101/2024.03.28.587125

HPV-positive head and neck squamous cell carcinoma cells lose viability during triggered myocyte lineage differentiation

Gendreizig, S.·Martinez-Ruiz, L.·Lopez-Rodriguez, A.·Pabla, H.·Hose, L.·Brasch, F.·Busche, T.·Escames, G.·Sudhoff, H.·Scholtz, L. U.·Todt, I.·Oppel, F.

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Abstract

Head and neck squamous cell carcinoma (HNSCC) is a highly malignant disease, and death rates have remained at approximately 50% for decades. New tumor-targeting treatment strategies are desperately needed. Using patient-derived tumor cells, we created an HNSCC differentiation model of HPV+ tumor cells from two patients. We observed a loss of malignant characteristics in differentiating cell culture conditions, including irregularly enlarged cell morphology, cell cycle arrest with downregulation of Ki67, and reduced cell viability. RNA-seq showed myocyte-like differentiation with upregulation of markers of myofibril assembly, including TPM1, TAGLN, and ACTA1. Immunofluorescence staining of differentiated and undifferentiated primary HPV+ HNSCC cells confirmed an upregulation of these markers and the formation of parallel actin fibers reminiscent of myoblast-lineage cells. Moreover, immunofluorescence of HPV+ tumor tissue revealed areas of cells co-expressing the identified markers of myofibril assembly, HPV surrogate marker p16, and stress-associated basal keratinocyte marker KRT17, indicating that the observed myocyte-like in vitro differentiation occurs in human tissue. A recent sarcoma study was able to turn rhabdomyosarcoma into muscle-like cells. We are the first to report that carcinoma cells can undergo a triggered myocyte differentiation. Our study suggests that the targeted myo-differentiation of tumor cells might be therapeutically valuable in HPV+ HNSCCs.

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Gendreizig, S., Martinez-Ruiz, L., Lopez-Rodriguez, A., Pabla, H., Hose, L., Brasch, F., Busche, T., Escames, G., Sudhoff, H., Scholtz, L. U., Todt, I., Oppel, F.. 2024-03-30. HPV-positive head and neck squamous cell carcinoma cells lose viability during triggered myocyte lineage differentiation. https://doi.org/10.1101/2024.03.28.587125

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