Recent evidence from the Di Vizio Laboratory indicates that fast migrating and metastatic amoeboid cancer cells undergoing non-apoptotic membrane blebbing can shed bioactive extracellular vesicles (EVs), namely large oncosomes, into the extracellular space due to their atypically large size in comparison with other classes of EVs.
Figure 1. Schematic hypothesis of large oncosome functions. Oncosomes shed from tumor cells condition the microenvironment in a manner that favors the production of soluble factors from stromal cells (Chin, 2009). Through degradation of the extracellular matrix, they could release endothelial permeabilization factors that facilitate intravasation. Oncosomes may also induce epigenetic changes and reprogram endothelial cells by transferring RNA, as has been hypothesized for other types of microvesicles. Because oncosomes can also induce migration of normal endothelial cells, circulating tumor-derived oncosomes might promote endothelial leakage, allowing extravasation and colonization of distant sites.
Specific areas of the study include:
- The role of large oncosomes in intercellular communication and in tumor growth and metastasis in prostate and breast cancers
- Molecular mechanisms regulating the function of specific miRNA cargo of large oncosomes in breast and lung cancer progression
- Molecular profiling of large oncosomes and other cancer-derived EVs by next generation sequencing and proteomics in prostate and breast cancer and in glioblastoma
- Molecular mechanisms and functional consequences of the internalization of large oncosomes in recipient cells
In a separate line of research, we are investigating the function of caveolin-1 in the prostate cancer stroma, with particular emphasis on the clinical significance of caveolin-1 loss with tumor progression and on the regulation of intracrine production of stromal androgens as a novel mechanism to cross-talk with the tumor cells.
Figure 2. miRNA export in EVs from tumorigenic and non-tumorigenic cells is finely regulated. Relative quantitation of the miRNAs with at least 1.5-fold expression change (red dotted lines) in EVs from tumorigenic RWPE-2 cells (left panel) versus cells themselves, and in EVs from non-tumorigenic RWPE-1 cells (right panel) versus cells. Red and green boxes show the top five or bottom five expressed miRNAs, respectively.