Exosomes in Breast Cancer - Mechanisms of Action and Clinical Potential.
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ABSTRACT:
SUBMITTER: Liu T
PROVIDER: S-EPMC8178200 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:In breast cancer (BC) the employment of sequencing technologies for metagenomic analyses has allowed not only the description of the overall metagenomic landscape but also the specific microbial changes and their functional implications. Most of the available data suggest that BC is related to bacterial dysbiosis in both the gut microenvironment and breast tissue. It is hypothesized that changes in the composition and functions of several breast and gut bacterial taxa may contribute to BC development and progression through several pathways. One of the most prominent roles of gut microbiota is the regulation of steroid-hormone metabolism, such as estrogens, a component playing an important role as risk factor in BC development, especially in postmenopausal women. On the other hand, breast and gut resident microbiota are the link in the reciprocal interactions between cancer cells and their local environment, since microbiota are capable of modulating mucosal and systemic immune responses. Several in vivo and in vitro studies show remarkable evidence that diet, probiotics and prebiotics could exert important anticarcinogenic effects in BC. Moreover, gut microbiota have an important role in the metabolism of chemotherapeutic drugs and in the activity of immunogenic chemotherapies since they are a potential dominant mediator in the response to cancer therapy. Then, the microbiome impact in BC is multi-factorial, and the gut and breast tissue bacteria population could be important in regulating the local immune system, in tumor formation and progression and in therapy response and/or resistance.
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Project description:Breast cancer can seriously disrupt a person's important life goals. As such, the ability to adjust one's goals may be critical for well-being. The present study investigated the relationships between disengagement/reengagement capacity and well-being among women with breast cancer, as well as several potential mechanisms (intrusive thoughts, life purpose, and physical activity) that could explain these relationships. The sample consisted of 230 women with early-stage (n?=?172) or late-stage (n?=?58) breast cancer, who were followed prospectively for 8 months. Well-being measures consisted of global mental health, perceived physical health, positive/negative affect, and sleep efficiency. Disengagement capacity did not predict any outcome variable. In contrast, reengagement capacity prospectively predicted changes in global mental health, positive affect, negative affect, sleep efficiency, life purpose, and physical activity. Life purpose mediated the prospective relationship between reengagement capacity and multiple aspects of well-being. The relationships between purpose and positive/negative affect were reciprocal over time. Results also suggested that physical activity is not a mediator, but is in fact a result of the effect of reengagement capacity on well-being. The results demonstrate that reengagement capacity is important for well-being among women with breast cancer.
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Project description:BackgroundThe situation faced by breast cancer patients, especially those with triple-negative breast cancer, is still grave. More effective therapeutic targets are needed to optimize the clinical management of breast cancer. Although collagen type VIII alpha 1 chain (COL8A1) has been shown to be downregulated in BRIP1-knockdown breast cancer cells, its clinical role in breast cancer remains unknown.MethodsGene microarrays and mRNA sequencing data were downloaded and integrated into larger matrices based on various platforms. Therefore, this is a multi-centered study, which contains 5048 breast cancer patients and 1161 controls. COL8A1 mRNA expression in breast cancer was compared between molecular subtypes. In-house immunohistochemistry staining was used to evaluate the protein expression of COL8A1 in breast cancer. A diagnostic test was performed to assess its clinical value. Furthermore, based on differentially expressed genes (DEGs) and co-expressed genes (CEGs) positively related to COL8A1, functional enrichment analyses were performed to explore the biological function and potential molecular mechanisms of COL8A1 underlying breast cancer.ResultsCOL8A1 expression was higher in breast cancer patients than in control samples (standardized mean difference = 0.79; 95% confidence interval [CI] 0.55-1.03). Elevated expression was detected in various molecular subtypes of breast cancer. An area under a summary receiver operating characteristic curve of 0.80 (95% CI 0.76-0.83) with sensitivity of 0.77 (95% CI 0.69-0.83) and specificity of 0.70 (95% CI 0.61-0.78) showed moderate capacity of COL8A1 in distinguishing breast cancer patients from control samples. Worse overall survival was found in the higher than in the lower COL8A1 expression groups. Intersected DEGs and CEGs positively related to COL8A1 were significantly clustered in the proteoglycans in cancer and ECM-receptor interaction pathways.ConclusionsElevated COL8A1 may promote the migration of breast cancer by mediating the ECM-receptor interaction and synergistically interplaying with DEGs and its positively related CEGs independently of molecular subtypes. Several genes clustered in the proteoglycans in cancer pathway are potential targets for developing effective agents for triple-negative breast cancer.
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Project description:Background: Breast cancer is one of the principal causes of death among women and there is a pressing need to develop novel and effective anti-cancer agents. Natural plant products have shown promising results as anti-cancer agents. Their effectiveness is reported as decreased toxicity in usage, along with safety and less recurrent resistances compared with hormonal targeting anti-cancer agents. Methods: A literature search was conducted for all English-language literature published prior to June 2020. The search was conducted using electronic databases, including PubMed, Embase, Web of Science, and Cochrane Library. The search strategy included keywords such as breast cancer, herbs, anti-cancer biologically active components, clinical research, chemotherapy drugs amongst others. Results: The literature provides documented evidence of the chemo-preventative and chemotherapeutic properties of Ginseng, garlic (Allium sativum), Black cohosh (Actaea racemose), Tumeric (Curcuma longa), Camellia sinenis (green tea), Echinacea, Arctium (burdock), Flaxseed (Linum usitatissimum) and Black Cumin (Nigella sativa). Conclusions: The nine herbs displayed anti-cancer properties and their outcomes and mechanisms of action include inhibition of cell proliferation, angiogenesis and apoptosis as well as modulation of key intracellular pathways. However, more clinical trials and cohort human studies should be conducted to provide key evidence of their medical benefits.
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Project description:Cancer cells efficiently transfer exosome contents (essentially mRNAs and microRNAs) to other cell types, modifying immune responses, cell growth, angiogenesis and metastasis. Here we analyzed the exosomes release by breast tumor cells with different capacities of stemness/metastasis based on CXCR4 expression, and evaluated their capacity to generate oncogenic features in recipient cells. Breast cancer cells overexpressing CXCR4 showed an increase in stemness-related markers, and in proliferation, migration and invasion capacities. Furthermore, recipient cells treated with exosomes from CXCR4-cells showed increased in the same abilities. Moreover, inoculation of CXCR4-cell-derived exosomes in immunocompromised mice stimulated primary tumor growth and metastatic potential. Comparison of nucleic acids contained into exosomes isolated from patients revealed a "stemness and metastatic" signature in exosomes of patients with worse prognosis. Finally, our data supported the view that cancer cells with stem-like properties show concomitant metastatic behavior, and their exosomes stimulate tumor progression and metastasis. Exosomes-derived nucleic acids from plasma of breast cancer patients are suitable markers in the prognosis of such patients.
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Project description:The potent actions of pigment epithelium-derived factor (PEDF) on tumour-associated cells, and its extracellular localization and secretion, stimulated research on this multifunctional serpin. Such studies have identified several PEDF receptors and downstream signalling pathways. Known cellular PEDF responses have expanded from the initial discovery that PEDF induces retinoblastoma cell differentiation to its anti-angiogenic, antitumorigenic and antimetastatic properties. Although the diversity of PEDF activities seems to be complex, they are consistent with the varied mechanisms that regulate this multimodal factor. If PEDF is to be used for cancer management, a deeper appreciation of its many functions and mechanisms of action is needed.
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Project description:Exosomes are nano-sized biovesicles released into surrounding body fluids upon fusion of multivesicular bodies and the plasma membrane. They were shown to carry cell-specific cargos of proteins, lipids, and genetic materials, and can be selectively taken up by neighboring or distant cells far from their release, reprogramming the recipient cells upon their bioactive compounds. Therefore, the regulated formation of exosomes, specific makeup of their cargo, cell-targeting specificity are of immense biological interest considering extremely high potential of exosomes as non-invasive diagnostic biomarkers, as well as therapeutic nanocarriers. In present review, we outline and discuss recent progress in the elucidation of the regulatory mechanisms of exosome biogenesis, the molecular composition of exosomes, and technologies used in exosome research. Furthermore, we focus on the potential use of exosomes as valuable diagnostic and prognostic biomarkers for their cell-lineage and state-specific contents, and possibilities as therapeutic vehicles for drug and gene delivery. Exosome research is now in its infancy, in-depth understanding of subcellular components and mechanisms involved in exosome formation and specific cell-targeting will bring light on their physiological activities.
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