Human papillomavirus-associated head and neck squamous cell carcinoma cells lose viability during triggered myocyte lineage differentiation.
Sarah GendreizigLaura Martínez-RuizAlba López-RodríguezHarkiren PablaLeonie HoseFrank BraschTobias BuscheGermaine EscamesHolger SudhoffLars Uwe ScholtzIngo TodtFelix OppelPublished in: Cell death & disease (2024)
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 strategies are desperately needed, and a previous report indicated the triggered differentiation of HPV-negative HNSCC cells to confer therapeutic benefits. Using patient-derived tumor cells, we created a similar 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. 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. We are the first to report that carcinoma cells can undergo a triggered myocyte-like differentiation, and our study suggests that the targeted differentiation of HPV+ HNSCCs might be therapeutically valuable.
Keyphrases
- cell cycle arrest
- induced apoptosis
- cell death
- single cell
- rna seq
- pi k akt
- high grade
- signaling pathway
- endoplasmic reticulum stress
- oxidative stress
- squamous cell carcinoma
- cell proliferation
- poor prognosis
- stem cells
- end stage renal disease
- mesenchymal stem cells
- cancer therapy
- peritoneal dialysis
- rectal cancer
- patient reported
- cell migration