Extracellular vesicles in cancer therapy.

Extracellular vesicles (EVs), including a variety of membrane-enclosed nanosized particles carrying cell-derived cargo, mediate a major type of intercellular communication in physiological and pathological processes. Both cancer and non-cancer cells secrete EVs, which can travel to and influence various types of cells at the primary tumor site as well as in distant organs. Tumor-derived EVs contribute to cancer cell plasticity and resistance to therapy, adaptation of tumor microenvironment, local and systemic vascular remodeling, immunomodulation, and establishment of pre-metastatic niches. Therefore, targeting the production, uptake, and function of tumor-derived EVs has emerged as a new strategy for stand-alone or combinational therapy of cancer. On the other hand, as EV cargo partially reflects the genetic makeup and phenotypic properties of the secreting cell, EV-based biomarkers that can be detected in biofluids are being developed for cancer diagnosis and for predicting and monitoring tumor response to therapy. Meanwhile, EVs from presumably safe sources are being developed as delivery vehicles for anticancer therapeutic agents and as anticancer vaccines. Numerous reviews have discussed the biogenesis and characteristics of EVs and their functions in cancer. Here, I highlight recent advancements in translation of EV research outcome towards improved care of cancer, including developments of non-invasive EV-based biomarkers and therapeutic agents targeting tumor-derived EVs as well as engineering of therapeutic EVs.

Wang SE 《-》

Extracellular Vesicles and Metastasis.

Secretion of cell contents through extracellular vesicles (EVs), such as exosomes and microvesicles, is a fundamental cell behavior. Compared with their normal counterparts, cancer cells are different in the amount and composition of EVs they secrete as a result of intrinsic and extrinsic (microenvironmental) alterations. Although EVs were originally recognized as a means to remove undesired cell components, recent studies show their critical role in mediating intercellular interaction through cargo transport. In cancer, EVs can be transferred between different cancer cell subpopulations and between cancer and normal cells localized inside and outside of the tumor. By regulating various aspects of cellular functions, EVs contribute to tumor heterogeneity and plasticity, vascular remodeling, cancer-niche coevolution, immunomodulation, and establishment of premetastatic niche, all of which are important to the process of metastasis. Recent discoveries on EV-mediated mechanisms lead to a new understanding of the multifaceted changes in tumor and nontumor tissues before and after cancer metastasis, paving the way for new therapeutic strategies.

Wang SE 《Cold Spring Harbor Perspectives in Medicine》

Extracellular Vesicles and Bone-Associated Cancer.

In this review, we describe the biology of extracellular vesicles (EV) and how they contribute to bone-associated cancers. Crosstalk between tumor and bone has been demonstrated to promote tumor and metastatic progression. In addition to direct cell-to-cell contact and soluble factors, such as cytokines, EVs mediate crosstalk between tumor and bone. EVs are composed of a heterogenous group of membrane-delineated vesicles of varying size range, mechanisms of formation, and content. These include apoptotic bodies, microvesicles, large oncosomes, and exosomes. EVs derived from primary tumors have been shown to alter bone remodeling and create formation of a pre-metastatic niche that favors development of bone metastasis. Similarly, EVs from marrow stromal cells have been shown to promote tumor progression. Additionally, EVs can act as therapeutic delivery vehicles due to their low immunogenicity and targeting specificity. EVs play critical roles in intercellular communication. Multiple classes of EVs exist based on size on mechanism of formation. In addition to a role in pathophysiology, EVs can be exploited as therapeutic delivery vehicles.

Dai J ，Shupp AB ，Bussard KM ，Keller ET ... -  《Current Osteoporosis Reports》

The key role of extracellular vesicles in the metastatic process.

Extracellular vesicles (EVs), including exosomes, have a key role in the paracrine communication between organs and compartments. EVs shuttle virtually all types of biomolecules such as proteins, lipids, nucleic acids, metabolites and even pharmacological compounds. Their ability to transfer their biomolecular cargo into target cells enables EVs to play a key role in intercellular communication that can regulate cellular functions such as proliferation, apoptosis and migration. This has led to the emergence of EVs as a key player in tumor growth and metastasis through the formation of "tumor niches" in target organs. Recent data have also been shown that EVs may transform the microenvironment of primary tumors thus favoring the selection of cancer cells with a metastatic behavior. The release of EVs from resident non-malignant cells may contribute to the metastatic processes as well. However, cancer EVs may induce malignant transformation in resident mesenchymal stem cells, suggesting that the metastatic process is not exclusively due to circulating tumor cells. In this review, we outline and discuss evidence-based roles of EVs in actively regulating multiple steps of the metastatic process and how we can leverage EVs to impair metastasis.

Zhao H ，Achreja A ，Iessi E ，Logozzi M ，Mizzoni D ，Di Raimo R ，Nagrath D ，Fais S ... -  《-》

Role of tumor‑derived extracellular vesicles in cancer progression and their clinical applications (Review).

Qiao F ，Pan P ，Yan J ，Sun J ，Zong Y ，Wu Z ，Lu X ，Chen N ，Mi R ，Ma Y ，Ji Y ... -  《-》