The precise mechanism underlying why disease-specific salivary biomarkers are present in the saliva remains unclear. Studies have shown that exosomes can stably reside in body fluids, including urine, blood, milk, and saliva. Thus, we believe exosomes provide a credible means for intercellular communication. Because salivary exosomes are released into the saliva via ductal or acinar cells, salivary gland cells may interact with circulating tumor exosomes in the vasculature and reflect this interaction in the exosomes secreted into the saliva. We found that PKH-labeled 231-derived exosome-like microvesicles were capable not only of protecting the PKH molecule from quenching by serum, but also labeling HSG cells. Thus, even though we do not show the transference of proteins or mRNA, this result suggests that 231-derived exosome-like microvesicles are capable of transferring their exosomal materials to HSG cells. Because we observed that only approximately half of the HSG cell populations were labeled, the heterogeneity of the cell line itself may contribute to this variation in exosome uptake. Thus, to examine whether the HSG cell population has variations in 231derived exosome-like microvesicle uptake, we introduced PKHlabeled 231-derived exosome-like microvesicles to HSG cells at various dilutions. Using fluorescence activated cell sorting we observed a decrease in HSG cell labeling as the concentration of the input PKH-labeled 231-derived exosomelike microvesicles decreased. This finding indicates that the concentration of the labeled 231-derived exosome-like microvesicles that is introduced and the random encounter and uptake of these microvesicles by the HSG cells results in the labeling of,Soyasaponin-Bb of the cells, rather than the heterogeneity of the HSG cell population. We also observed that the interactions between 231-derived exosome-like microvesicles and HSG cells induced an overall up-regulation of their total RNA levels at the transcriptional level. However, we were unable to detect any obvious phenotypic alterations to the HSG cells. Thus, while the rationale is unclear and beyond the scope of this study, we reason that there could be multitude of reasons that are at the molecular and biological levels that may be worthwhile to pursue for future studies. The literature suggests several possible mechanisms by which exosomes can enter a cell, transfer material, and activate transcription. First, exosomes are capable of fusing with cell membranes and directly entering the cytoplasm. Alternatively, exosomes can enter a cell passively via clathrin and receptormediated processes. Studies have identified micro-RNA and transcription factors in exosomes of various origins. Thus, exosomes may transfer their contents to induce transcription. Exosomes have also been proposed to interact with a target cell in a juxtacrine fashion, by ectodomain cleavage leading to exosomal fragments acting as ligands, or direct fusion with the target cell. Juxtacrine communication and ectodomain cleavage are thought to Soyosaponin-Ac allow exosomal proteins to interact with the target cell receptors, leading to cell activation. Here, we showed that the interplay between 231-derived exosome-like microvesicles and HSG cells in vitro alters the HSG-derived exosome-like microvesicles proteomically. Several models have been proposed in regards to exosome uptake and protein trafficking that may be useful for future investigations into their mechanism. Due to the heterogeneity of exosomal proteins, which range from transmembrane proteins to chaperones, exosomal protein packaging may be both endosomal sorting complex required for transport dependent and/or independent depending on cellular localization.