Extracellular Vesicles: The Landscape in the Progression, Diagnosis, and Treatment of Triple-Negative Breast Cancer.

Triple-negative breast cancer (TNBC) is a heterogeneous subtype of breast cancer (BC) with diverse biological behavior, high aggressiveness, and poor prognosis. Extracellular vesicles (EVs) are nano-sized membrane-bound vesicles secreted by nearly all cells, and are involved in physiological and pathological processes. EVs deliver multiple functional cargos into the extracellular space, including proteins, lipids, mRNAs, non-coding RNAs (ncRNAs), and DNA fragments. Emerging evidence confirms that EVs enable pro-oncogenic secretome delivering and trafficking for long-distance cell-to-cell communication in shaping the tumor microenvironment (TME). The transferred tumor-derived EVs modify the capability of invasive behavior and organ-specific metastasis in recipient cells. In addition, TNBC cell-derived EVs have been extensively investigated due to their promising potential as valuable biomarkers for diagnosis, monitoring, and treatment evaluation. Here, the present review will discuss the recent progress of EVs in TNBC growth, metastasis, immune regulation, as well as the potential in TNBC diagnosis and treatment application, hoping to decipher the advantages and challenges of EVs for combating TNBC.

Dong M ，Liu Q ，Xu Y ，Zhang Q ... -  《Frontiers in Cell and Developmental Biology》

Secreted Non-Coding RNAs: Functional Impact on the Tumor Microenvironment and Clinical Relevance in Triple-Negative Breast Cancer.

Di Agostino S ，Vahabi M ，Turco C ，Fontemaggi G ... -  《-》

Extracellular vesicles-associated miRNAs in triple-negative breast cancer: from tumor biology to clinical relevance.

Berti FCB ，Tofolo MV ，Nunes-Souza E ，Marchi R ，Okano LM ，Ruthes M ，Rosolen D ，Malheiros D ，Fonseca AS ，Cavalli LR ... -  《-》

Extracellular Vesicles in Triple-Negative Breast Cancer: Immune Regulation, Biomarkers, and Immunotherapeutic Potential.

Das K ，Paul S ，Ghosh A ，Gupta S ，Mukherjee T ，Shankar P ，Sharma A ，Keshava S ，Chauhan SC ，Kashyap VK ，Parashar D ... -  《Cancers》

Effect of tumor-derived extracellular vesicle-shuttled lncRNA MALAT1 on proliferation, invasion and metastasis of triple-negative breast cancer by regulating macrophage M2 polarization via the POSTN/Hippo/YAP axis.

Triple-negative breast cancer (TNBC) is the deadliest subtype of breast cancer (BC). Tumor-derived extracellular vesicles (EVs) trigger tumor progression by promoting M2 polarization. Some lncRNAs can be encapsulated into EVs for intercellular communication. Herein, we investigated the mechanism of TNBC-derived EV-shuttled lncRNA MALAT1 on macrophage polarization/tumorigenesis. BC-associated targeted EV-derived lncRNAs were screened. Tumor tissues/tissues adjacent to cancer of TNBC patients, and blood samples of all subjects were collected. MALAT1/POSTN mRNA levels in tumor tissues/tissues adjacent to cancer, and MALAT1 expression in EVs and its correlation with TNBC patient overall survival were assessed by RT-qPCR/Kaplan-Meier survival analysis/log-rank test. TNBC patient M2 infiltration was detected by flow cytometry. MALAT1/POSTN levels in EVs/macrophages were regulated by transfection. Hippo/YAP activation was determined by Western blot. Nude mouse xenograft model was established and metastasis was detected by H&E staining. MALAT1/POSTN were up-regulated and correlated with M2 infiltration/poor prognosis in TNBC patients. TNBC-derived EVs induced M2 polarization. MALAT1 was highly expressed in TNBC-derived EVs and could be transferred to macrophages via EVs to induce M2 polarization. POSTN overexpression diminished the inhibitory effect of MALAT1 knockdown on M2 markers. EVs activated the Hippo/YAP pathway in macrophages. The Hippo/YAP pathway inhibition abrogated the effect of POSTN overexpression on M2 marker expression. TNBC-EV-derived MALAT1 facilitated M2 polarization, and thus promoting occurrence and metastasis of TNBC in vitro and in vivo. TNBC-EV-derived MALAT1 activated the Hippo/YAP axis by up-regulating POSTN, thereby inducing M2 polarization to promote TNBC occurrence and metastasis in vivo.

Wang X ，Jian Q ，Zhang Z ，Gu J ，Wang X ，Wang Y ... -  《Translational Oncology》