Homogenates of feces from healthy volunteers and cultured HT-29 cells (human colorectal cancer cell line) were treated with RNase. Total RNA was extracted from RNase-treated cells (cultured HT-29 or colonic epithelial cells isolated from feces) and exosomes isolated from cell-free HT-29 culture media or feces. Additionally, free RNA from both conditions was isolated. Samples were then analyzed for the presence of selected microRNA species by real-time Inhibitors,research,lifescience,medical RT-PCR. Investigators found that free microRNA was completely degraded by the addition of RNase whereas cellular microRNA was resistant to RNase degradation. Interestingly, exosomal microRNAs were partially (HT-29

cell-derived) or completely (feces-derived) resistant to RNase degradation. Among the microRNA species analyzed in this study was miR-21, which has elevated levels in colorectal cancer tissue compared with normal colonic tissue; however, no differences have been noted with respect to early versus advanced stage colorectal cancer (17). Nonetheless, if validated in larger,

appropriately-powered Inhibitors,research,lifescience,medical studies, findings as such could pave the way to the development of highly sensitive and specific and potentially cost-effective colorectal Inhibitors,research,lifescience,medical cancer screening tests, particularly in regions of the world with relatively scarce endoscopic resources. In this context, exosomes may represent a biomarker of cellular injury or atypia. However, others have demonstrated that these and other cellular vesicles may provide important insights in the pathogenesis of certain diseases, including cancer. Recent interest has focused on their capacity to shuttle cellular components from one cell to another and alter cellular fate. Transfer of membrane receptors Inhibitors,research,lifescience,medical between cells has been reported as has transfer of HIV and prions (18)-(22). Our group has demonstrated that murine lung tissue-derived check details microvesicles induce co-cultured bone marrow cells to express pulmonary

epithelial cell-specific Inhibitors,research,lifescience,medical mRNA and protein, likely through the transfer of a microRNA or protein-based transcription factor contained within microvesicles (14),(23). When transplanted into lethally-irradiated mice, microvesicle-modified marrow cells preferentially engraft the lung as functioning type II pneumocytes (unpublished below findings). In vitro culture studies done by our group and others have demonstrated that tumor-derived microvesicles can transfer determinants to non-malignant cells (18) and that human prostate cancer tissue is capable of inducing tissue specific mRNA transcription in human bone marrow cells (24),(25). In a similar vein, Al-Nedawia et al. reported that microvesicles produced from human cancer cell lines can transfer EGFR to human umbilical vein endothelial cells, in vitro (26). Cancer cell line xenografts in SCID mice that were treated to block microvesicle production had reduced tumor angiogenesis and growth, suggesting a role of tumor-derived microvesicles in cancer progression.