The Tumor-Suppressive Role Of Secreted Maspin Via The Exosomes

A TUMOR-SUPPRESSIVE ROLE OF MASPIN SECRETED VIA THE EXOSOMESbyIVORY DEANDecember 2014Advisor: Shijie Sheng, Ph.D. Major: Cancer BiologyDegree: Doctor of PhilosophyThis dissertation highlights several novel findings. Maspin has been consistentlydetected in the conditioned media of maspin-expressing cells of normal and tumorbreast, prostate and lung origin. Furthermore, extracellular maspin has beendemonstrated to have anti-tumor effects. Interestingly, maspin has been reported ascargo of the exosomes, which highlights one of the secretion mechanisms of maspin.Maspin secretion as an exosomal molecule was verified by electron microscopy, atomicforce microscopy, light scattering dynamic analysis and immunoblot analysis.The data showed that exosomes derived from the non-malignant cell lines havetwo distinct populations that do no overlap in their size distributions. Based on the size distribution and the electron microscopy analysis, it is likely that exosomes derived fromthe non-malignant cells are aggregated exosomes.. In contrast, tumor cell-derivedexosomes comprised a population of broader size distribution.To understand how secreted maspin may contribute to tumor suppression, it iscritical to understand how maspin is regulated at the step of protein trafficking. The datashowed that maspin is secreted by dual mechanisms, as free and exosomal protein,