Dual role for p16 in the metastasis process of HPV positive head and neck cancers.
Several studies show that human papillomavirus (HPV) positive head and neck cancers (HNSCC) are typically characterized by low tumor and high regional node stages, intrinsically indicating high local metastatic potential. Despite this, the distant metastasis rates of HPV positive and negative HNSCC are similar. To date, majority of the studies focus on molecular characterization of HPV positive disease and on treatment outcome. Here we assessed the biological mechanisms of metastasis by combining in vitro and in vivo head and neck carcinoma xenograft models with patient data. We provide experimental evidence for a dual role of p16, a surrogate marker for HPV infections, in the metastasis process of HNSCC. We found that p16 regulates the invasiveness and metastatic potential of HNSCC cells by impairing angiogenesis. In parallel, we found that p16 is regulating the nodal spread by mediating lymphatic vessel formation through the upregulation of integrins. These findings not only provide understanding of the biology of the different dissemination patterns but also suggest that inhibition of lymphangiogenesis in HPV positive cancers and inhibition of angiogenesis in HPV negative cancers can form a treatment strategy against metastasis.
['Dok|Rüveyda|R|', 'Glorieux|Mary|M|', 'Holacka|Karolina|K|', 'Bamps|Marieke|M|', 'Nuyts|Sandra|S|']
D000368:Aged D002294:Carcinoma, Squamous Cell D002465:Cell Movement D019941:Cyclin-Dependent Kinase Inhibitor p16 D005260:Female D006258:Head and Neck Neoplasms D006801:Humans D042583:Lymphangiogenesis D008207:Lymphatic Metastasis D008297:Male D008875:Middle Aged D009361:Neoplasm Invasiveness D009389:Neovascularization, Pathologic D027383:Papillomaviridae D030361:Papillomavirus Infections D000077195:Squamous Cell Carcinoma of Head and Neck D042461:Vascular Endothelial Growth Factor A
P16 Metastasis HPV Head and neck cancer Angiogenesis Lymphangiogenesis