Extracellular vesicles in ovarian cancer chemoresistance, metastasis, and immune evasion.

Chemoresistance and metastasis are the major challenges for the current ovarian cancer treatment. Understanding the mechanisms of ovarian cancer progression and metastasis is critically important for developing novel therapies. The advances in extracellular vesicles (EVs) research in recent years have attracted extensive attention. EVs contain a variety of proteins, RNAs, DNAs, and metabolites. Accumulating evidence indicates that ovarian cancer cells secrete a large amount of EVs, playing an important role in tumor progression and recurrence. In the microenvironment of ovarian tumor, EVs participate in the information transmission between stromal cells and immune cells, promoting the immune escape of ovarian cancer cells and facilitating cancer metastasis. Here, we review the recent advances of EVs in chemoresistance, mechanisms of metastasis, and immune evasion of ovarian cancer. Furthermore, we also discuss the challenges of EV research and future application of EVs as promising biomarker sources in response to therapy and in therapy-delivery approaches for ovarian cancer patients.

Tian W ，Lei N ，Zhou J ，Chen M ，Guo R ，Qin B ，Li Y ，Chang L ... -  《Cell Death & Disease》

Role of Extracellular Vesicles in Epithelial Ovarian Cancer: A Systematic Review.

Lucidi A ，Buca D ，Ronsini C ，Tinari S ，Bologna G ，Buca D ，Leombroni M ，Liberati M ，D'Antonio F ，Scambia G ，Lanuti P ，Petrillo M ... -  《INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES》

FAP(high) α-SMA(low) cancer-associated fibroblast-derived SLPI protein encapsulated in extracellular vesicles promotes ovarian cancer development via activation of PI3K/AKT and downstream signaling pathways.

Ovarian cancer is the most lethal gynecological malignancy worldwide with high metastasis and poor prognosis rates. Cancer-associated fibroblasts (CAFs), a heterogeneous population of cells that constitutes a major component of the tumor microenvironment, secrete extracellular vesicles (EVs) loading with proteins, lipids, and RNAs to promote tumorigenesis. However, the specific roles of CAF-derived proteins contained in EVs in ovarian cancer remain poorly understood at present. Using the gene expression microarray analysis, we identified a list of dysregulated genes between the α-SMA+ CAF and FAP+ CAF subpopulations, from which secretory leukocyte protease inhibitor (SLPI) was chosen for further validation. Quantitative PCR, western blot, immunohistochemistry, and enzyme-linked immunosorbent assays were used to assess SLPI expression in ovarian cancer cells, tissues, CAFs, and EVs. Additionally, we evaluated the effects of exogenous SLPI on proliferation, migration, invasion, and adhesion of ovarian cancer cells in vitro. Our results showed SLPI protein was upregulated in CAFs, particularly in the FAPhigh α-SMAlow CAF subpopulation, and associated with increased tumor grade and decreased overall survival (OS). Importantly, CAF-derived SLPI protein could be encapsulated in EVs for delivery to ovarian cancer cells, thus facilitating cell proliferation, migration, invasion, and adhesion via activating the PI3K/AKT and downstream signaling pathways. Moreover, high plasma expression of SLPI encapsulated in EVs was closely correlated with tumor stage in ovarian cancer patients. Our collective results highlight an oncogenic role of plasma EV-encapsulated SLPI secreted by CAFs in tumor progression for the first time, supporting its potential utility as a prognostic biomarker of ovarian cancer.

Sun L ，Ke M ，Wang X ，Yin M ，Wei J ，Xu L ，Tian X ，Wang F ，Zhang H ，Fu S ，Zhang C ... -  《-》

Unraveling the extracellular vesicle network: insights into ovarian cancer metastasis and chemoresistance.

Dai W ，Zhou J ，Chen T 《Molecular Cancer》

Extracellular vesicles as a novel approach for breast cancer therapeutics.

Breast cancer (BC) still lacks effective management approaches to control metastatic and therapy-resistant disease. Extracellular vesicles (EVs), with a diameter of 50-1000 nm, are secreted by all types of living cells, are protected by a lipid bilayer and encapsulate biological cargos including RNAs, proteins and lipids. They play an important role in intercellular communications and are significantly associated with pathological conditions. Accumulating evidence indicates that cancer cells secrete EVs and communicate with neighboring cells within the tumor microenvironment (TME), which plays an important role in BC metastasis, immune escape and chemoresistance, thus providing a new therapeutic window. EVs can stimulate angiogenesis and extracellular matrix remodeling, establish premetastatic niches, inhibit immune response and promote cancer metastasis. Recent advances have demonstrated that EVs are a potential therapeutic target or carrier and have emerged as promising strategies for BC treatment. In this review, we summarize the role of EVs in BC metastasis, chemoresistance and immune escape, which provides the foundation for developing novel therapeutic approaches. We also focus on current EV-based drug delivery strategies in BC and EV cargo-targeted BC therapy and discuss the limitations and future perspectives of EV-based drug delivery in BC.

Lee Y ，Graham P ，Li Y 《-》