Dual role for p16 in the metastasis process of HPV positive head and neck cancers

Molecular Cancer

Letter to the Editor

Mary Glorieux¹  Marieke Bamps¹  Karolina Holacka¹  Rüveyda Dok¹  Sandra Nuyts² 

[1] Department of Oncology, Laboratory of Experimental Radiotherapy, KU Leuven, University of Leuven, 3000, Leuven, Belgium;Department of Oncology, Laboratory of Experimental Radiotherapy, KU Leuven, University of Leuven, 3000, Leuven, Belgium;Department of Radiation Oncology, Leuven Cancer Institute, UH Leuven, Herestraat 49 box 815, 3000, Leuven, Belgium;

关键词: HPV;    P16;    Head and neck cancer;    Metastasis;    Angiogenesis;    Lymphangiogenesis;   

DOI  :  10.1186/s12943-017-0678-8

 received in 2017-04-24, accepted in 2017-06-14,  发布年份 2017

来源: Springer

【 摘 要 】

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.

【 授权许可】

CC BY   
© The Author(s). 2017