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Project description:Adipocytes regulate breast cancer aggressiveness through exosomes that encode patient metabolic status.
2022-06-09 | PXD029369 | Pride
Project description:Adipocyte-derived extracellular vesicles promote breast cancer progression in type 2 diabetes
| PRJNA773780 | ENA
Project description:Disseminated breast cancer cells have the capacity to metastasise to the bone marrow and reside in a dormant state within the mesenchymal stem cell niche. Research has focussed on paracrine signalling factors, such as soluble proteins, within the microenvironment. However, it is now clear extracellular vesicles secreted by resident mesenchymal stem cells into this microenvironment also play a key role in the initiation of dormancy. Dormancy encourages reduced cell proliferation and migration, while upregulating cell adhesion, thus retaining the cancer cells within the bone marrow microenvironment. Here, MCF7 breast cancer cells were treated with mesenchymal stem cell-derived extracellular vesicles, resulting in reduced migration in two-dimensional and three-dimensional culture, with reduced cell proliferation and enhanced adhesion, collectively supporting cancer cell dormancy.
| S-EPMC6311537 | biostudies-literature
Project description:BackgroundExtracellular vesicles (EVs) are mediators between cancer cells and other types of cells, such as tumor-associated macrophages (TAMs), in the tumor microenvironment. EVs can remodel the tumor microenvironment and regulate tumor progression. However, the underlying molecular mechanism of these interactions remains unclear.MethodsFirst, we explored the effect of TAMs on the survival prognosis of patients with ovarian cancer. Next, we isolated EVs derived from ovarian cancer cells (OV-EVs) through ultracentrifugation and analyzed the capacity of OV-EVs to regulate macrophage polarization in ovarian tumors and in whole peripheral blood. Moreover, we explored the roles of OV-EVs-induced macrophages in tumor progression through in vitro and in vivo assays.ResultsOV-EVs were encapsulated by macrophages and induced the polarization of macrophages toward the M2 phenotype. Moreover, OV-EVs-induced M2 macrophages promoted angiogenesis and cancer progression both in vitro and in vivo. In addition, OV-EVs-induced macrophages increased the expression level of VEGF and increased the expression level of VEGFR in tumors, which resulted in angiogenesis in ovarian cancer.ConclusionsThe present study demonstrated that OV-EVs induce M2 polarization in macrophages and promote the progression of ovarian cancer. This study provides novel insight into the mechanism of ovarian cancer progression.
| S-EPMC11344305 | biostudies-literature
Project description:Breast cancer is one of the most serious and terrifying threats to the health of women. Recent studies have demonstrated that interaction among cancer cells themselves and those with other cells, including immune cells, in a tumor microenvironment potentially and intrinsically regulate and determine cancer progression and metastasis. Small extracellular vesicles (sEVs), a type of lipid-bilayer particles derived from cells, with a size of less than 200 nm, are recognized as one form of important mediators in cell-to-cell communication. sEVs can transport a variety of bioactive substances, including proteins, RNAs, and lipids. Accumulating evidence has revealed that sEVs play a crucial role in cancer development and progression, with a significant impact on proliferation, invasion, and metastasis. In addition, sEVs systematically coordinate physiological and pathological processes, such as coagulation, vascular leakage, and stromal cell reprogramming, to bring about premetastatic niche formation and to determine metastatic organ tropism. There are a variety of oncogenic factors in tumor-derived sEVs that mediate cellular communication between local stromal cells and distal microenvironment, both of which are important in cancer progression and metastasis. Tumor-derived sEVs contain substances that are similar to parental tumor cells, and as such, sEVs could be biomarkers in cancer progression and potential therapeutic targets, particularly for predicting and preventing future metastatic development. Here, we review the mechanisms underlying the regulation by tumor-derived sEVs on cancer development and progression, including proliferation, metastasis, drug resistance, and immunosuppression, which coordinately shape the pro-metastatic microenvironment. In addition, we describe the application of sEVs to the development of cancer biomarkers and potential therapeutic modalities and discuss how they can be engineered and translated into clinical practice.
| S-EPMC9736664 | biostudies-literature
Project description:White adipose tissue (WAT) is involved in long-term energy storage and represents 10-15% of total body weight in healthy humans. WAT secretes many peptides (adipokines), hormones and steroids involved in its homeostatic role, especially in carbohydrate-lipid metabolism regulation. Recently, adipocyte-derived extracellular vesicles (AdEVs) have been highlighted as important actors of intercellular communication that participate in metabolic responses to control energy flux and immune response. In this review, we focus on the role of AdEVs in the cross-talks between the different cellular types composing WAT with regard to their contribution to WAT homeostasis and metabolic complications development. We also discuss the AdEV cargoes (proteins, lipids, RNAs) which may explain AdEV's biological effects and demonstrate that, in terms of proteins, AdEV has a very specific signature. Finally, we list and suggest potential therapeutic strategies to modulate AdEV release and composition in order to reduce their deleterious effects during the development of metabolic complications associated with obesity.
| S-EPMC7916840 | biostudies-literature
Project description:The post-transcriptional control of gene expression is a complex and evolving field in adipocyte biology, with the premise that the delivery of microRNA (miRNA) species to the obese adipose tissue may facilitate weight loss. Cells shed extracellular vesicles (EVs) that may deliver miRNAs as intercellular messengers. However, we know little about the miRNA profile of EVs secreted by adipocytes during postnatal development. Here, we defined the miRNA cargo of EVs secreted by mouse adipocytes in two distinct phases of development: on postnatal day 6, when adipocytes are lipolytic and thermogenic, and on postnatal day 56, when adipocytes have active lipogenesis. EVs were collected from cell culture supernatants, and their miRNA profile was defined by small RNA sequencing. The most abundant miRNA of mouse adipocyte-derived EVs was mmu-miR-148a-3p. Adipocyte EVs on postnatal day 6 were hallmarked with mmu-miR-98-5p, and some miRNAs were specific to this developmental stage, such as mmu-miR-466i-5p and 12 novel miRNAs. Adipocytes on postnatal day 56 secreted mmu-miR-365-3p, and 16 miRNAs were specific to this developmental stage. The miRNA cargo of adipocyte EVs targeted gene networks of cell proliferation, insulin signaling, interferon response, thermogenesis, and lipogenesis. We provided here a database of miRNAs secreted by developing mouse adipocytes, which may be a tool for further studies on the regulation of gene networks that control mouse adipocyte development.
| S-EPMC11311276 | biostudies-literature
Project description:Cancer immunotherapies have shown clinical success in various types of tumors but the patient response rate is low, particularly in breast cancer. Here we report that malignant breast cancer cells can transfer active TGF-β type II receptor (TβRII) via tumor-derived extracellular vesicles (TEV) and thereby stimulate TGF-β signaling in recipient cells. Up-take of extracellular vesicle-TβRII (EV-TβRII) in low-grade tumor cells initiates epithelial-to-mesenchymal transition (EMT), thus reinforcing cancer stemness and increasing metastasis in intracardial xenograft and orthotopic transplantation models. EV-TβRII delivered as cargo to CD8+ T cells induces the activation of SMAD3 which we demonstrated to associate and cooperate with TCF1 transcription factor to impose CD8+ T cell exhaustion, resulting in failure of immunotherapy. The levels of TβRII+ circulating extracellular vesicles (crEV) appears to correlate with tumor burden, metastasis and patient survival, thereby serve as a non-invasive screening tool to detect malignant breast tumor stages. Thus, our findings not only identify a possible mechanism by which breast cancer cells can promote T cell exhaustion and dampen host anti-tumor immunity, but may also identify a target for immune therapy against the most devastating breast tumors.
| S-EPMC9343611 | biostudies-literature
Project description:Recently, the emerging roles of adipocyte-derived extracellular vesicles (EVs) linking obesity and its comorbidities have been recognized. In obese subjects, adipocytes are having hypertrophic growth and are under stressed. The dysfunction adipocytes dysregulate the assembly of the biological components in the EVs including exosomes. This article critically reviews the current findings on the impact of obesity on the exosomal cargo contents that induce the pathophysiological changes. Besides, this review also summarizes the understanding on how obesity affects the biogenesis of adipocyte-derived exosomes and the exosome secretion. Furthermore, the differences of the exosomal contents in different adipose depots, and the impact of obesity on the exosomes that are derived from the stromal vascular fraction such as the adipose tissue macrophages and adipocyte-derived stem cells will also be discussed. The current development and potential application of exosome-based therapy will be summarized. This review provides crucial information for the design of novel exosome-based therapy for the treatment of obesity and its comorbidities.
| S-EPMC8531905 | biostudies-literature
Project description:Metastasis is associated with poor prognosis in breast cancer patients. Not all cancer cells within a tumor are capable of metastasizing. The microRNA-200 (miR-200) family, which regulates the mesenchymal-to-epithelial transition, is enriched in the serum of patients with metastatic cancers. Ectopic expression of miR-200 can confer metastatic ability to poorly metastatic tumor cells in some settings. Here, we investigated whether metastatic capability could be transferred between metastatic and nonmetastatic cancer cells via extracellular vesicles. miR-200 was secreted in extracellular vesicles from metastatic murine and human breast cancer cell lines, and miR-200 levels were increased in sera of mice bearing metastatic tumors. In culture, murine and human metastatic breast cancer cell extracellular vesicles transferred miR-200 microRNAs to nonmetastatic cells, altering gene expression and promoting mesenchymal-to-epithelial transition. In murine cancer and human xenograft models, miR-200-expressing tumors and extracellular vesicles from these tumors promoted metastasis of otherwise weakly metastatic cells either nearby or at distant sites and conferred to these cells the ability to colonize distant tissues in a miR-200-dependent manner. Together, our results demonstrate that metastatic capability can be transferred by the uptake of extracellular vesicles.
| S-EPMC4348969 | biostudies-literature