Ricerc@Sapienza

Human papillomavirus (HPV) is the causative agent of squamous cell carcinoma. The infection itself is not sufficient for the transformation of the infected cells, even if the integration of the virus in the host cell genome that cause genetic rearrangements, the activation of proto- oncogenes and other events, can generate genomic instability and increase the risk of neoplastic transformation. Tumor microenvironment (TME) is strongly correlated with chronic inflammation. Persistent infection is one possible cause of establishing chronic inflammation. Expression of cytokines and chemokines and other molecular mediators is altered thereby recruiting and differentiating into TME immune cells with a pro-tumoral phenotype. Extracellular vesicles (EVs) can load and deliver a specific package of mediators (e.g. mRNAs, microRNAs, proteins) and consequently, cancer can take advantage of this process. Based on preliminary data showing a wide deregulation of inflammatory microenvironment in prototypical cellular models of high-risk mucosal HPV-positive or cutaneous HPV-positive cells, the purpose of the project is to better characterize EVs into TME in these models. Our objective is to find mRNAs and microRNAs specifically loaded into EVs and to define their possible role principally in their cargo transfer into primary keratinocytes.