Dataset Information

The Microbiome of Aseptically Collected Human Breast Tissue in Benign and Malignant Disease.

ABSTRACT: Globally breast cancer is the leading cause of cancer death among women. The breast consists of epithelium, stroma and a mucosal immune system that make up a complex microenvironment. Growing awareness of the role of microbes in the microenvironment recently has led to a series of findings important for human health. The microbiome has been implicated in cancer development and progression at a variety of body sites including stomach, colon, liver, lung, and skin. In this study, we assessed breast tissue microbial signatures in intraoperatively obtained samples using 16S rDNA hypervariable tag sequencing. Our results indicate a distinct breast tissue microbiome that is different from the microbiota of breast skin tissue, breast skin swabs, and buccal swabs. Furthermore, we identify distinct microbial communities in breast tissues from women with cancer as compared to women with benign breast disease. Malignancy correlated with enrichment in taxa of lower abundance including the genera Fusobacterium, Atopobium, Gluconacetobacter, Hydrogenophaga and Lactobacillus. This work confirms the existence of a distinct breast microbiome and differences between the breast tissue microbiome in benign and malignant disease. These data provide a foundation for future investigation on the role of the breast microbiome in breast carcinogenesis and breast cancer prevention.

SUBMITTER: Hieken TJ

PROVIDER: S-EPMC4971513 | biostudies-literature | 2016 Aug

REPOSITORIES: biostudies-literature

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The Microbiome of Aseptically Collected Human Breast Tissue in Benign and Malignant Disease.

Hieken Tina J TJ Chen Jun J Hoskin Tanya L TL Walther-Antonio Marina M Johnson Stephen S Ramaker Sheri S Xiao Jian J Radisky Derek C DC Knutson Keith L KL Kalari Krishna R KR Yao Janet Z JZ Baddour Larry M LM Chia Nicholas N Degnim Amy C AC

Scientific reports 20160803

Globally breast cancer is the leading cause of cancer death among women. The breast consists of epithelium, stroma and a mucosal immune system that make up a complex microenvironment. Growing awareness of the role of microbes in the microenvironment recently has led to a series of findings important for human health. The microbiome has been implicated in cancer development and progression at a variety of body sites including stomach, colon, liver, lung, and skin. In this study, we assessed breas ...[more]

PMID: 27485780

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Project description:BackgroundTo study the expression pattern, localisation and potential clinical significance of aquaporin water channels (AQP) both in prostate cancer (PC) cell lines and in benign and malignant human prostate tissue.MethodsThe AQP transcript and protein expression of HPrEC, LNCaP, DU-145 and PC3 cell lines was investigated using reverse transcriptase polymerase chain reaction (RT-PCR) and immunofluorescence (IF) microscopy labelling. Immunohistochemistry (IHC) was performed to assess AQP protein expression in surgical specimens of benign prostatic hyperplasia as well as in PC. Tissue mRNA expression of AQPs was quantified by single-step reverse transcriptase quantitative polymerase chain reaction (qPCR). Relative gene expression was determined using the 40-?CT method and correlated to clinicopathological parameters.ResultsTranscripts of AQP 1, 3, 4, 7, 8, 10 and 11 were expressed in all four cell lines, while AQP 9 transcripts were not detected in malignant cell lines. IF microscopy confirmed AQP 3, 4, 5, 7 and 9 protein expression. IHC revealed highly heterogeneous AQP 3 protein expression in PC specimens, with a marked decrease in expression in tumours of increasing malignancy. Loss of AQP 9 was shown in PC specimens. mRNA expression of AQP3 was found to be negatively correlated to PSA levels (??=?-?0.354; p =?0.013), D'Amico risk stratification (??=?-?0.336; p =?0.012), ISUP grade (??=?-?0.321; p =?0.017) and Gleason score (??=?-?0.342; p =?0.011).ConclusionsThis is the first study to systematically characterize human prostate cell lines, benign prostatic hyperplasia and PC in relation to all 13 members of the AQP family. Our results indicate the differential expression of several AQPs in benign and malignant prostate tissue. A significant correlation was observed between AQP 3 expression and tumour grade, with progressive loss in more malignant tumours. Taken together, AQPs may play a role in the progression of PC and AQP expression patterns may serve as a prognostic marker.

Project description:Few preclinical models accurately depict normal human prostate tissue or primary prostate cancer (PCa). In vitro systems typically lack complex cellular interactions among structured prostatic epithelia and a stromal microenvironment, and genetic and molecular fidelity are concerns in both in vitro and in vivo models. 'Tissue slice cultures' (TSCs) provide realistic preclinical models of diverse tissues and organs, but have not been fully developed or widely utilized for prostate studies. Problems encountered include degeneration of differentiated secretory cells, basal cell hyperplasia, and poor survival of PCa. Here, we optimized, characterized, and applied a TSC model of primary human PCa and benign prostate tissue that overcomes many deficiencies of current in vitro models. Tissue cores from fresh prostatectomy specimens were precision-cut at 300??m and incubated in a rotary culture apparatus. The ability of varied culture conditions to faithfully maintain benign and cancer cell and tissue structure and function over time was evaluated by immunohistological and biochemical assays. After optimization of the culture system, molecular and cellular responses to androgen ablation and to piperlongumine (PL), purported to specifically reduce androgen signaling in PCa, were investigated. Optimized culture conditions successfully maintained the structural and functional fidelity of both benign and PCa TSCs for 5 days. TSCs exhibited androgen dependence, appropriately undergoing ductal degeneration, reduced proliferation, and decreased prostate-specific antigen expression upon androgen ablation. Further, TSCs revealed cancer-specific reduction of androgen receptor and increased apoptosis upon treatment with PL, validating data from cell lines. We demonstrate a TSC model that authentically recapitulates the structural, cellular, and genetic characteristics of the benign and malignant human prostate, androgen dependence of the native tissue, and cancer-specific response to a potentially new therapeutic for PCa. The work described herein provides a basis for advancing the experimental utility of the TSC model.

Project description:Background Elastography is a promising way to evaluate tissue differences regarding stiffness, and the stiffness of the malignant breast lesions increased at the lesion margin. However, there is a lack of data on the value of the shear wave elastography (SWE) parameters of the surrounding tissue (shell) of different diameter on the diagnosis of benign and malignant breast lesions. Therefore, the purpose of our study was to evaluate the diagnostic performance of shell elasticity in the diagnosis of benign and malignant breast lesions using SWE. Methods Between September 2016 and June 2017, women with breast lesions underwent both conventional ultrasound (US) and SWE. Elastic values of the lesions peripheral tissue were determined according to the shell size, which was automatically drawn along the edge of the lesion using the following software guidelines: (1): 1?mm; (2): 2?mm; and (3): 3?mm. Quantitative elastographic features of the inner lesions and shell, including the elasticity mean (Emean), elasticity maximum (Emax), and elasticity minimum (Emin), were calculated using an online-available software. The receiver operating characteristic curves (ROCs) of the elastographic features was analyzed to assess the diagnostic performance, and the area under curve (AUC) of each elastographic feature was obtained. Logistic regression analysis was used to predict significant factors of malignancy, permitting the design of predictive models. Results This prospective study included 63 breast lesions of 63 women. Of the 63 lesions, 33 were malignant and 30 were benign. The diagnostic performance of Emax-3shell was the highest (AUC?=?0.76) with a sensitivity of 60.6% and a specificity of 83.3%. According to stepwise logistic regression analysis, the Emax-3shell and the Emin-3shell were significant predictors of malignancy (p?<?0.05). The AUC of the predictive equation was 0.86. Conclusions SWE features, particularly the combination of Emax-3shell and Emin-3shell can improve the diagnosis of breast lesions.

Dataset Information

The Microbiome of Aseptically Collected Human Breast Tissue in Benign and Malignant Disease.

Publications

The Microbiome of Aseptically Collected Human Breast Tissue in Benign and Malignant Disease.

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