In an attempt to conceptualize the process of cancer formation, Hanahan and Weinberg [2000] have outlined six universal characteristics of tumorigenesis, and labelled them as the "hallmarks of cancer". These hallmarks include; unlimited proliferation, evading growth suppressors, resisting cell death, replicative immortality, inducing angiogenesis, initiating invasion and metastasis. Cancer cell signalling is crucial for initiating and controlling cellular pathways that are involved in these hallmarks. The intricate network of communication between cancer cells and other cancer or non-cancer cells is still being investigated, and is yet to be fully understood. Initially it was proposed that the main form of communication between cells within the tumour microenvironment are soluble growth factors, and gap junctions. Then, researchers reported another form of cell-to-cell communication, through the release of spherical particles called exosomes. It is believed that these exosomes enable communication through the transfer of active components from the releasing cell, and off-loading it into the recipient cell. As researchers continue to examine the development of the cancer hallmarks and the pathways involved, it became evident that cancer cell-derived exosomes play a major role in almost all of them. This review will examine the role played by cancer cell-derived exosomes in development of cancer.

Background: The placenta is an abundant source of mesenchymal stem/stromal cells (MSC), but our understanding of their functional properties remains limited. We previously created a placental-derived chorionic MSC (CMSC) cell line to overcome the difficulties associated with conducting extensive ex vivo optimization and experimental work on primary cells. The aim of this study was to characterize the migratory behavior of the CMSC29 cell line in vitro. Methods: Stimulators of MSC migration, including two cytokines, stromal cell-derived factor-1α (SDF-1α) and hepatocyte growth factor (HGF), and a pharmacological agent, valproic acid (VPA), were tested for their ability to stimulate CMSC29 cell migration. Assessment of cell migration was performed using the xCELLigence Real-Time Cell Analyzer (RTCA). Results: There was no significant increase in CMSC29 cell migration towards serum free medium with increasing concentration gradients of SDF-1α or HGF. In contrast, treating CMSC29 cells with VPA alone significantly increased their migration towards serum free medium. Conclusions: Immortalized CMSC29 cells retain important properties of primary CMSC, but their migratory properties are altered. CMSC29 cells do not migrate in response to factors that reportedly stimulate primary MSC/CMSC migration. However, CMSC29 increase their migration in response to VPA treatment alone. Further studies are needed to determine the mechanism by which VPA acts alone to stimulate CMSC29 migration. Still, this study provides evidence that VPA pre-treatment may improve the benefits of cell-based therapies that employ certain MSC sub-types.

Background: To initiate tissue repair, mesenchymal stem/stromal cells (MSCs) must enter the blood stream, migrate to the targeted area, cross the endothelial barrier and home to the damaged tissue. This process is not yet fully understood in humans and thus, the aim of this study was to develop an ex vivo placental vessel perfusion method to examine human MSC movement from a blood vessel into human tissue. This will provide a better understanding of MSC migration, movement through the endothelial barrier and engraftment into target tissue, in a setting that more closely represents the in vivo state, compared with conventional in vitro human cell culture models. Moreover, important similarities and differences to animal experimental model systems may be revealed by this method. Methods: Human placental hTERT transformed MSC lines were labelled with live-cell fluorescence dyes, and then perfused into term human placental blood vessel. After labelled MSCs were perfused into the vessel, the vessel was dissected from the placenta and incubated at cell growth conditions. Following incubation, the vessel was washed thoroughly to remove unattached, labelled MSCs and then snap frozen for sectioning. After sectioning, immunofluorescence staining of the endothelium was carried out to detect if labelled MSCs crossed the endothelial barrier. Results: Twelve placental vessel perfusions were successfully completed. In eight of the twelve perfused vessels, qualitative assessment of immunofluorescence in sections (n=20, 5 µm sections/vessel) revealed labelled MSCs had crossed the endothelial barrier. Conclusions: The human placental ex vivo vessel perfusion method could be used to assess human MSC migration into human tissue. Cells of the MSC lines were able to adhere and transmigrate through the endothelial barrier in a manner similar to that of leukocytes. Notably, cells that transmigrated remained in close proximity to the endothelium, which is consistent with the reported MSC vascular niche in placental blood vessels.