Small extracellular vesicle-mediated metabolic reprogramming: from tumors to pre-metastatic niche formation.

Metastasis, the spread of a tumor or cancer from the primary site of the body to a secondary site, is a multi-step process in cancer progression, accounting for various obstacles in cancer treatment and most cancer-related deaths. Metabolic reprogramming refers to adaptive metabolic changes that occur in cancer cells in the tumor microenvironment (TME) to enhance their survival ability and metastatic potential. Stromal cell metabolism also changes to stimulate tumor proliferation and metastasis. Metabolic adaptations of tumor and non-tumor cells exist not only in the TME but also in the pre-metastatic niche (PMN), a remote TME conducive for tumor metastasis. As a novel mediator in cell-to-cell communication, small extracellular vesicles (sEVs), which have a diameter of 30-150 nm, reprogram metabolism in stromal and cancer cells within the TME by transferring bioactive substances including proteins, mRNAs and miRNAs (microRNAs). sEVs can be delivered from the primary TME to PMN, affecting PMN formation in stroma rewriting, angiogenesis, immunological suppression and matrix cell metabolism by mediating metabolic reprogramming. Herein, we review the functions of sEVs in cancer cells and the TME, how sEVs facilitate PMN establishment to trigger metastasis via metabolic reprogramming, and the prospective applications of sEVs in tumor diagnosis and treatment. Video Abstract.

Jiang C ，Jiang Z ，Sha G ，Wang D ，Tang D ... -  《Cell Communication and Signaling》

Tumor-Derived Small Extracellular Vesicles Involved in Breast Cancer Progression and Drug Resistance.

Feng L ，Guo L ，Tanaka Y ，Su L ... -  《INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES》

Small Extracellular Vesicles: Key Forces Mediating the Development and Metastasis of Colorectal Cancer.

Zhang W ，Hu X ，Jiang Z 《Cells》

Small extracellular vesicles: from promoting pre-metastatic niche formation to therapeutic strategies in breast cancer.

Breast cancer is the most common cancer in females, and to date, the mortality rate of breast cancer metastasis cannot be ignored. The metastasis of breast cancer is a complex, staged process, and the pattern of metastatic spread is not random. The pre-metastatic niche, as an organ-specific home for metastasis, is a favourable environment for tumour cell colonization. As detection techniques improve, the role of the pre-metastatic niche in breast cancer metastasis is being uncovered. sEVs (small extracellular vesicles) can deliver cargo, which is vital for the formation of pre-metastatic niches. sEVs participate in multiple aspects of creating a distant microenvironment to promote tumour invasion, including the secretion of inflammatory molecules, immunosuppression, angiogenesis and enhancement of vascular permeability, as well as regulation of the stromal environment. Here, we discuss the multifaceted mechanisms through which breast cancer-derived sEVs contribute to pre-metastatic niches. In addition, sEVs as biomarkers and antimetastatic therapies are also discussed, particularly their use in transporting exosomal microRNAs. The study of sEVs may provide insight into immunotherapy and targeted therapies for breast cancer, and we also provide an overview of their potential role in antitumour metastasis. Video Abstract.

Chen X ，Feng J ，Chen W ，Shao S ，Chen L ，Wan H ... -  《Cell Communication and Signaling》

Extracellular vesicle-mediated pre-metastatic niche formation via altering host microenvironments.

The disordered growth, invasion and metastasis of cancer are mainly attributed to bidirectional cell-cell interactions. Extracellular vesicles (EVs) secreted by cancer cells are involved in orchestrating the formation of pre-metastatic niches (PMNs). Tumor-derived EVs mediate bidirectional communication between tumor and stromal cells in local and distant microenvironments. EVs carrying mRNAs, small RNAs, microRNAs, DNA fragments, proteins and metabolites determine metastatic organotropism, enhance angiogenesis, modulate stroma cell phenotypes, restructure the extracellular matrix, induce immunosuppression and modify the metabolic environment of organs. Evidence indicates that EVs educate stromal cells in secondary sites to establish metastasis-supportive microenvironments for seeding tumor cells. In this review, we provide a comprehensive overview of PMN formation and the underlying mechanisms mediated by EVs. Potential approaches to inhibit cancer metastasis by inhibiting the formation of PMNs are also presented.

Li Y ，Zheng Y ，Tan X ，Du Y ，Wei Y ，Liu S ... -  《Frontiers in Immunology》