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

Gendreizig S, Martinez-Ruiz L, López-Rodríguez A, Pabla H, Hose L, Brasch F, Busche T, Escames G, Sudhoff H, Scholtz L-U, Todt I, et al. (2024)
bioRxiv.

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Autor*in
Gendreizig, SarahUniBi ; Martinez-Ruiz, Laura; López-Rodríguez, Alba; Pabla, Harkiren; Hose, LeonieUniBi ; Brasch, Frank; Busche, TobiasUniBi; Escames, Germaine; Sudhoff, HolgerUniBi ; Scholtz, Lars-UweUniBi; Todt, IngoUniBi; Oppel, FelixUniBi
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Abstract / Bemerkung

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.

Erscheinungsjahr
2024
Zeitschriftentitel
bioRxiv
Page URI
https://pub.uni-bielefeld.de/record/2991403

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Gendreizig S, Martinez-Ruiz L, López-Rodríguez A, et al. HPV-positive head and neck squamous cell carcinoma cells lose viability during triggered myocyte lineage differentiation. bioRxiv. 2024.
Gendreizig, S., Martinez-Ruiz, L., López-Rodríguez, A., Pabla, H., Hose, L., Brasch, F., Busche, T., et al. (2024). HPV-positive head and neck squamous cell carcinoma cells lose viability during triggered myocyte lineage differentiation. bioRxiv. https://doi.org/10.1101/2024.03.28.587125
Gendreizig, Sarah, Martinez-Ruiz, Laura, López-Rodríguez, Alba, Pabla, Harkiren, Hose, Leonie, Brasch, Frank, Busche, Tobias, et al. 2024. “HPV-positive head and neck squamous cell carcinoma cells lose viability during triggered myocyte lineage differentiation”. bioRxiv.
Gendreizig, S., Martinez-Ruiz, L., López-Rodríguez, A., Pabla, H., Hose, L., Brasch, F., Busche, T., Escames, G., Sudhoff, H., Scholtz, L. - U., et al. (2024). HPV-positive head and neck squamous cell carcinoma cells lose viability during triggered myocyte lineage differentiation. bioRxiv.
Gendreizig, S., et al., 2024. HPV-positive head and neck squamous cell carcinoma cells lose viability during triggered myocyte lineage differentiation. bioRxiv.
S. Gendreizig, et al., “HPV-positive head and neck squamous cell carcinoma cells lose viability during triggered myocyte lineage differentiation”, bioRxiv, 2024.
Gendreizig, S., Martinez-Ruiz, L., López-Rodríguez, A., Pabla, H., Hose, L., Brasch, F., Busche, T., Escames, G., Sudhoff, H., Scholtz, L.-U., Todt, I., Oppel, F.: HPV-positive head and neck squamous cell carcinoma cells lose viability during triggered myocyte lineage differentiation. bioRxiv. (2024).
Gendreizig, Sarah, Martinez-Ruiz, Laura, López-Rodríguez, Alba, Pabla, Harkiren, Hose, Leonie, Brasch, Frank, Busche, Tobias, Escames, Germaine, Sudhoff, Holger, Scholtz, Lars-Uwe, Todt, Ingo, and Oppel, Felix. “HPV-positive head and neck squamous cell carcinoma cells lose viability during triggered myocyte lineage differentiation”. bioRxiv (2024).
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