Influence of hypoxia on proliferation and migration of HPV-positive and HPV-negative Head-and-neck cancer cell lines (HNSCC)

Introduction:

In Patients with Human Papilloma Virus associated (HPV+) oropharyngeal squamous cell carcinomas (OPSCC) lymph node metastasis are more frequently at diagnosis compared to patients with HPV-negative (HPV-) OPSCC. Viral oncoproteins stabilize the hypoxia inducible factor 1 (HIF-1a), which affects signaling pathways involved in invasion and migration. Cellular proteins E-cadherin and β-Catenin are involved in the formation of cell-cell-contacts and regulation of cell growth and proliferation (β-Catenin). A reduced expression of both proteins increases the tendency to metastasize. In this study we examine proliferation and migration of HPV+ and HPV- cells related to the role of HIF-1a and it's interaction with E-cadherin and β-Catenin.

Methods:

Proliferation and migration of HPV+ and HPV- cell lines were analyzed with scratch assays. Protein expression of E-Cadherin, β-Catenin and HIF-1a was analyzed by Western blotting and immunofluorescence microscopy.

Results:

We recently showed different proliferation and migration pattern in two HPV+ and two HPV- HNSCC cell lines (p = 0.018) related to hypoxia-pathway activation. Recent examinations with other HPV+ and HPV- cell lines confirm this finding. Two (HPV-) lung cancer cell lines showed reduced proliferation and migration under hypoxia, too, which conforms to HPV- HNSCC cell lines. In contrast, HPV+ cell lines showed uninfluenced migration and proliferation under hypoxia.

Conclusion:

Due to different carcinogenic processes, HPV+ and HPV- cell lines differ in their cellular adaption to hypoxia. In HPV+ cells, a constitutional activation of the hypoxia-pathway seems to enhance migration before in HPV- cells migration is activated by other factors, which might explain differences in lymph node metastasis in OPSCC.

Publication History

Publication Date:
23 April 2019 (online)