defines a set of proangiogenic mRNAs and microRNAs implicated in tumor progression and metas- tases. Our results define a specific source of cancer stem cell-derived MVs that contribute to triggering the angiogenic switch and coordinating metastatic diffusion during tumor progression.

cells induced in vitro and in vivo angiogenesis and favored lung metastasis. These properties were ascribed only to the microvesicles released from the CD105 positive cell fraction. Microvesicles derived from CD105 positive renal cancer stem cells differ in their content of mRNAs and miRNAs with respect to the CD105 negative renal cancer cell population. In particular, CD105 positive MVs contained several proangiogenic mRNAs. The proangiogenic effect of CD105 positive MVs can be ascribed to their ability to induce endothelial cell growth, organization, invasion of matrix and resistance to apoptosis. The gene ontology analysis of predicted target genes indicated that CD105 positive microvesicles shuttled a selected pattern of miRNAs that may modulate several biological functions relevant for cell growth, regulation of transcription, cell matrix adhesion and synthesis of macromolecules. Microvesicles create a receptive microenvironment to coordinate metastatic diffusion. These microvesicles, by enhancing tumor vascularization and contributing to the establishment of a premetastatic niche, may sustain an unfavorable outcome of the tumor.