Epstein-Barr Virus Dedifferentiates Adipocytes and Contributes to the Reconstruction of Tumor Microenvironment(2/3)

The Epstein-Barr virus (EBV), a member of the herpesvirus family, infects andestablished life-long persistence in over 95% of the world’s adult population. Mostinfections with EBV go unnoticed or produce only very mild symptom, however, itcan be associated with the development of several types of human malignancy,including undifferentiated nasopharyngeal carcinoma (NPC) and a variety oflymphoepithelioma-like carcinomas (LELC). Remote metastasis is detected in overone-third of NPC cases and the most frequent metastasis location of NPC is bone, anadipocyte-dominant region. Additionally, several types of EBV-associated LELCgrow in the anatomical vicinity of fat tissues, such as breast, salivary gland, andkidney. It is now recognized that tumor-associated adipocytes are active contributorsto tumor progression. To determine whether EBV orchestrates the interactionsbetween adipose tissues and tumor cells to create a pro-tumorigenicmicroenvironment, we conducted experiments with the involvement of EBV, humanadipocytes, and cancer cells. In summary, our data showed that EBV could infectprimary adipocytes and preadipocytes and the infection with EBV triggered lipolysisand dedifferentiated mature adipocytes to fibroblast-like cells. Immunohistochemicalanalysis found positive immunoreactivity of EBV-encoded early antigen D in adiposetissues located at the invasive front of salivary LELC and bone metastatic NPC.Further, mediators released from EBV-stimulated adipocytes increased cancer cellproliferation and this growth-promoting effect might work through the activation ofmTOR/p70S6K1 pathway. In the present study, we aim to clarify the role of EBV inadipocyte biology and understand how EBV and adipocytes coordinately reconstructthe tumor microenvironment to benefit virus and tumor cells themselves.