Early studies first proposed that exosomes are secreted to discard membrane proteins. However, more recent studies have shown that exosomes also contain antigens that are capable of triggering a biological immune response by activating T lymphocytes, natural killer cells, and dendritic cells. Zitvogel et al. showed that dendritic cell-derived exosomes stimulate T-cellmediated anti-tumor immune responses in mice. Dendritic cellderived exosomes were also found to express high levels of MHC class I and class-II peptides that trigger T-cell responses leading to tumor rejection. Studies have also suggested that exosomes secreted by metastatic tumors provide interactions between the tumor front and distal host site, promoting tumor invasion by transporting RNA between cells, suppressing immune responses, and promoting angiogenesis. These previous studies demonstrated that exosomes are durable for travel through body fluids and capable of intercellular communication. However, whether salivary gland cells are able to Campesterol interact and take up tumor-derived exosome-like microvesicles has not been examined. Moreover, whether the interplay between tumor-derived exosome-like microvesicles and salivary gland cells alters salivary gland-derived exosome-like microvesicles is unknown. Because studies have shown that salivary gland cells readily secrete exosome-like microvesicles, we hypothesized that tumor-derived exosome-like microvesicles interact with salivary gland cells and alter the composition of their secreted exosome-like microvesicles in an in vitro setting. Using an in vitro breast cancer model, we investigated whether breast cancerderived exosome-like microvesicles can communicate with salivary gland cells and if this interaction alters the exosome-like microvesicles released by salivary gland cells. Saliva is an effective, non-invasive biofluid for the detection of various diseases, such as pancreatic, oral, and breast cancer. In this study, we demonstrated that the interplay between 231derived exosome-like microvesicles and HSG cell altered HSG derived exosome-like microvesicles. We showed that both HSG and 231 cells are capable of secreting exosome-like microvesicles encapsulating protein and mRNA. In addition, we observed that the PKH-labeled 231-derived exosome-like microvesicles were able to label HSG cells in the presence of serum. Moreover, the interplay between 231-derived exosomes and HSG cells activated the HSG cell transcriptional machinery,Soyasaponin-Be inducing an up-regulation of total cellular RNA. We also discovered that interactions between HSG cells and 231-derived exosome-like microvesicles altered the HSG-derived exosome-like microvesicles both proteomically and transcriptomically. The examination of isolates from the culture media of 231 and HSG cells showed that both cell lines secreted exosome-like microvesicles in abundance. Isolates from both 231 and HSG cells were identified as exosome-like microvesicles due to their size and morphology. In addition, the exosomal marker tetraspanin CD63 was found in both 231- and HSG-derived exosome-like microvesicles. The size differences between exosomelike microvesicle and cell lysate CD63 may be due to the glycosylation-prone nature of this membrane protein. Moreover, amylase protein was found in HSG-derived exosomelike microvesicles and the cell lysates, indicating that HSG cells have acinar cell-like characteristics. We also observed that HSG readily secreted exosome-like microvesicles encapsulating both mRNA and proteins, suggesting that these HSG cells are capable of secreting biomarker-enriched exosome-like microvesicles. These results are consistent with the findings of GonzalesBegne et al., who found 914 total parotid gland-derived exosomal proteins, and with our previous work in which we found that salivary exosome-like microvesicles contain proteins and functional mRNA.