Dataset Information

The Biology of Exosomes in Breast Cancer Progression: Dissemination, Immune Evasion and Metastatic Colonization.

ABSTRACT: In recent decades, the study of exosome biology has gained growing interest, representing an active area of cancer research with many potential clinical applications. Exosomes are small lipid bilayer particles released by cells with pleiotropic functions that have been reported to regulate the complex intracellular pathway involved in all steps of breast cancer development-from initiation to progression toward a metastatic dissemination. Particularly, the role of these microvesicles has been explored in metastasis, which represents the leading cause of breast cancer morbidity and mortality worldwide. Reports highlight that the plasticity of breast cancer cells, fundamental for the establishment of distant metastasis, may be in part attributed to exosome-carried signals shared between adjacent cells and long-distance cells in the body. In the present review, we will discuss the functions of exosomes in the metastatic breast cancer process and secondary site outgrowth. The possibility to decode the exosome functions in advanced diseases may offer new opportunities for early detection, molecular targeted therapies and exosome-based therapeutics in breast cancer.

SUBMITTER: Giordano C

PROVIDER: S-EPMC7465598 | biostudies-literature | 2020 Aug

REPOSITORIES: biostudies-literature

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The Biology of Exosomes in Breast Cancer Progression: Dissemination, Immune Evasion and Metastatic Colonization.

Giordano Cinzia C La Camera Giusi G Gelsomino Luca L Barone Ines I Bonofiglio Daniela D Andò Sebastiano S Catalano Stefania S

Cancers 20200805 8

In recent decades, the study of exosome biology has gained growing interest, representing an active area of cancer research with many potential clinical applications. Exosomes are small lipid bilayer particles released by cells with pleiotropic functions that have been reported to regulate the complex intracellular pathway involved in all steps of breast cancer development-from initiation to progression toward a metastatic dissemination. Particularly, the role of these microvesicles has been exp ...[more]

PMID: 32764376

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Project description:Metastatic castration-resistant prostate cancer (mCRPC) with low androgen receptor (AR) and without neuroendocrine signaling, termed double-negative prostate cancer (DNPC), is increasingly prevalent in patients treated with AR signaling inhibitors and is in need of new biomarkers and therapeutic targets. Candidate genes enriched in DNPC were determined using differential gene expression analysis of discovery and validation cohorts of mCRPC biopsies. Laboratory studies were carried out in human mCRPC organoid cultures, prostate cancer (PCa) cell lines, and mouse xenograft models. Epigenetic studies were carried out in a rapid autopsy cohort. Dickkopf-1 (DKK1) expression is increased in DNPC relative to prostate-specific antigen (PSA)-expressing mCRPC in the Stand Up to Cancer/Prostate Cancer Foundation discovery cohort (11.2 v 0.28 reads per kilobase per million mapped reads; q < 0.05; n = 117) and in the University of Washington/Fred Hutchinson Cancer Research Center cohort (9.2 v 0.99 fragments per kilobase of transcript per million mapped reads; P < .0001). DKK1 expression can be regulated by activated Wnt signaling in vitro and correlates with activating canonical Wnt signaling mutations and low PSA mRNA in mCRPC biopsies (P < .05). DKK1 hypomethylation was associated with increased DKK1 mRNA expression (Pearson r = -0.66; P < .0001) in a rapid autopsy cohort (n = 7). DKK1-high mCRPC biopsies are infiltrated with significantly higher numbers of quiescent natural killer (NK) cells (P < .005) and lower numbers of activated NK cells (P < .0005). Growth inhibition of the human PCa model PC3 by the anti-DKK1 monoclonal antibody DKN-01 depends on the presence of NK cells in a severe combined immunodeficient xenograft mouse model. These results support DKK1 as a contributor to the immunosuppressive tumor microenvironment of DNPC. These data have provided the rationale for a clinical trial targeting DKK1 in mCRPC (ClinicalTrials.gov identifier: NCT03837353).

Dataset Information

The Biology of Exosomes in Breast Cancer Progression: Dissemination, Immune Evasion and Metastatic Colonization.

Publications

The Biology of Exosomes in Breast Cancer Progression: Dissemination, Immune Evasion and Metastatic Colonization.

Similar Datasets

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