Journal of Mammary Gland Biology and Neoplasia最新文献

{"title":"Single-Cell Transcription Mapping of Murine and Human Mammary Organoids Responses to Female Hormones.","authors":"Jenelys Ruiz Ortiz, Steven M Lewis, Michael Ciccone, Deeptiman Chatterjee, Samantha Henry, Adam Siepel, Camila O Dos Santos","doi":"10.1007/s10911-023-09553-x","DOIUrl":"10.1007/s10911-023-09553-x","url":null,"abstract":"<p><p>During female adolescence and pregnancy, rising levels of hormones result in a cyclic source of signals that control the development of mammary tissue. While such alterations are well understood from a whole-gland perspective, the alterations that such hormones bring to organoid cultures derived from mammary glands have yet to be fully mapped. This is of special importance given that organoids are considered suitable systems to understand cross species breast development. Here we utilized single-cell transcriptional profiling to delineate responses of murine and human normal breast organoid systems to female hormones across evolutionary distinct species. Collectively, our study represents a molecular atlas of epithelial dynamics in response to estrogen and pregnancy hormones.</p>","PeriodicalId":16413,"journal":{"name":"Journal of Mammary Gland Biology and Neoplasia","volume":"29 1","pages":"3"},"PeriodicalIF":3.0,"publicationDate":"2024-01-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10827859/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139576155","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Toward Characterizing Lymphatic Vasculature in the Mammary Gland During Normal Development and Tumor-Associated Remodeling","authors":"Petra Dahms, T. Lyons","doi":"10.1007/s10911-023-09554-w","DOIUrl":"https://doi.org/10.1007/s10911-023-09554-w","url":null,"abstract":"","PeriodicalId":16413,"journal":{"name":"Journal of Mammary Gland Biology and Neoplasia","volume":"25 1","pages":"1-12"},"PeriodicalIF":2.5,"publicationDate":"2024-01-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139437553","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Single-cell Analysis Reveals Inter- and Intratumour Heterogeneity in Metastatic Breast Cancer","authors":"Baptiste Hamelin, Milan M. S. Obradović, Atul Sethi, Michal Kloc, Simone Münst, Christian Beisel, Katja Eschbach, Hubertus Kohler, Savas Soysal, Marcus Vetter, Walter P. Weber, Michael B. Stadler, Mohamed Bentires-Alj","doi":"10.1007/s10911-023-09551-z","DOIUrl":"https://doi.org/10.1007/s10911-023-09551-z","url":null,"abstract":"<p>Metastasis is the leading cause of cancer-related deaths of breast cancer patients. Some cancer cells in a tumour go through successive steps, referred to as the metastatic cascade, and give rise to metastases at a distant site. We know that the plasticity and heterogeneity of cancer cells play critical roles in metastasis but the precise underlying molecular mechanisms remain elusive. Here we aimed to identify molecular mechanisms of metastasis during colonization, one of the most important yet poorly understood steps of the cascade. We performed single-cell RNA-Seq (scRNA-Seq) on tumours and matched lung macrometastases of patient-derived xenografts of breast cancer. After correcting for confounding factors such as the cell cycle and the percentage of detected genes (PDG), we identified cells in three states in both tumours and metastases. Gene-set enrichment analysis revealed biological processes specific to proliferation and invasion in two states. Our findings suggest that these states are a balance between epithelial-to-mesenchymal (EMT) and mesenchymal-to-epithelial transitions (MET) traits that results in so-called partial EMT phenotypes. Analysis of the top differentially expressed genes (DEGs) between these cell states revealed a common set of partial EMT transcription factors (TFs) controlling gene expression, including <i>ZNF750</i>, <i>OVOL2</i>, <i>TP63</i>, <i>TFAP2C</i> and <i>HEY2</i>. Our data suggest that the TFs related to EMT delineate different cell states in tumours and metastases. The results highlight the marked interpatient heterogeneity of breast cancer but identify common features of single cells from five models of metastatic breast cancer.</p>","PeriodicalId":16413,"journal":{"name":"Journal of Mammary Gland Biology and Neoplasia","volume":"22 1","pages":""},"PeriodicalIF":2.5,"publicationDate":"2023-12-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138561900","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"TGFß1 Stimulates Lymphatic Endothelial Cells to Produce IL7 and IL15, Which Act as Chemotactic Factors for Breast Cancer Cells with Mesenchymal Properties.","authors":"Nikolina Giotopoulou, Wenyang Shi, Malgorzata Maria Parniewska, Wenwen Sun, Jonas Fuxe","doi":"10.1007/s10911-023-09552-y","DOIUrl":"10.1007/s10911-023-09552-y","url":null,"abstract":"<p><p>The lymphatic system is a major gateway for tumor cell dissemination but the mechanisms of how tumor cells gain access to lymphatic vessels are not completely understood. Breast cancer cells undergoing epithelial-mesenchymal transition (EMT) gain invasive and migratory properties. Overexpression of the cytokine transforming growth factor β1 (TGFβ1), a potent inducer of EMT, is frequently detected in the tumor microenvironment and correlates with invasion and lymph metastasis. Recently, we reported that TGFβ1 stimulated breast cancer cells with mesenchymal properties to migrate in a targeted fashion towards the lymphatic system via CCR7/CCL21-mediated chemotaxis, similar to dendritic cells during inflammation. Here, we aimed to identify additional chemotactic factors and corresponding receptors that could be involved in guiding breast cancer cells through the lymphatic system. Through a combination of RNA sequencing analysis, database screening and invasion assays we identified IL7/IL7R and IL15/IL15R as pairs of chemokines and receptors with potential roles in promoting chemotactic migration of breast cancer cells with mesenchymal properties towards the lymphatics. The results demonstrate the capacity of TGFβ1 to orchestrate crosstalk between tumor cells and lymphatic endothelial cells and warrant further studies to explore the roles of IL7 and IL15 in promoting lymph metastasis of breast cancer.</p>","PeriodicalId":16413,"journal":{"name":"Journal of Mammary Gland Biology and Neoplasia","volume":"28 1","pages":"25"},"PeriodicalIF":2.5,"publicationDate":"2023-12-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10700205/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138487790","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A molecular toolbox to study progesterone receptor signaling.","authors":"Marleen T Aarts, Muriel Wagner, Tanne van der Wal, Antonius L van Boxtel, Renée van Amerongen","doi":"10.1007/s10911-023-09550-0","DOIUrl":"10.1007/s10911-023-09550-0","url":null,"abstract":"<p><p>Progesterone receptor (PR) signaling is required for mammary gland development and homeostasis. A major bottleneck in studying PR signaling is the lack of sensitive assays to measure and visualize PR pathway activity both quantitatively and spatially. Here, we develop new tools to study PR signaling in human breast epithelial cells. First, we generate optimized Progesterone Responsive Element (PRE)-luciferase constructs and demonstrate that these new reporters are a powerful tool to quantify PR signaling activity across a wide range of progesterone concentrations in two luminal breast cancer cell lines, MCF7 and T47D. We also describe a fluorescent lentiviral PRE-GFP reporter as a novel tool to visualize PR signaling at the single-cell level. Our reporter constructs are sensitive to physiological levels of progesterone. Second, we show that low background signaling, and high levels of PR expression are a prerequisite for robustly measuring PR signaling. Increasing PR expression by transient transfection, stable overexpression in MCF7 or clonal selection in T47D, drastically improves both the dynamic range of luciferase reporter assays, and the induction of endogenous PR target genes as measured by qRT-PCR. We find that the PR signaling response differs per cell line, target gene and hormone concentration used. Taken together, our tools allow a more rationally designed approach for measuring PR signaling in breast epithelial cells.</p>","PeriodicalId":16413,"journal":{"name":"Journal of Mammary Gland Biology and Neoplasia","volume":"28 1","pages":"24"},"PeriodicalIF":2.5,"publicationDate":"2023-11-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10687192/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138451617","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Fourteenth Annual ENBDC Workshop: Methods in Mammary Gland Biology and Breast Cancer.","authors":"Silke Blair Chalmers, Tanne van der Wal, Silvia Fre, Jos Jonkers","doi":"10.1007/s10911-023-09549-7","DOIUrl":"10.1007/s10911-023-09549-7","url":null,"abstract":"<p><p>The fourteenth annual workshop of the European Network for Breast Development and Cancer (ENBDC) on Methods in Mammary Gland Biology and Breast Cancer was held on April 26th - 29th in Weggis, Switzerland. For the first time, early career researchers organised and took part in an additional ECR workshop on the 26th of April, which was received with great enthusiasm. The topics of the main workshop included mammary branching and morphogenesis, novel experimental systems (model organisms), systemic influences on tumour progression and the tumour microenvironment. Novel and recent findings were shared across excellent oral and poster presentations.</p>","PeriodicalId":16413,"journal":{"name":"Journal of Mammary Gland Biology and Neoplasia","volume":"28 1","pages":"22"},"PeriodicalIF":2.5,"publicationDate":"2023-10-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10558360/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41176478","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"High-fat diet, but not duration of lactation, increases mammary gland lymphatic vessel function and subsequent growth of inflammatory breast cancer cells.","authors":"Wintana Balema, Janelle Morton, Richard A Larson, Li Li, Fred Christian Velasquez, Natalie W Fowlkes, Savitri Krishnamurthy, Bisrat G Debeb, Eva Sevick-Muraca, Wendy A Woodward","doi":"10.1007/s10911-023-09548-8","DOIUrl":"10.1007/s10911-023-09548-8","url":null,"abstract":"<p><p>Inflammatory breast cancer (IBC) presents as rapid-onset swelling and breast skin changes caused by tumor emboli in the breast and breast skin lymphatics. IBC has been linked with obesity and duration of breastfeeding, but how these factors affect IBC tumor progression is not clear. We modeled the simultaneous effects of diet and weaning in mice on in vivo lymphatic function; on IBC tumor growth; and on aspects of the mammary gland microenvironment before and after IBC (SUM149) xenograft inoculation. We hypothesized that weaning status and diet would have synergistic effects on lymphatic function and the breast microenvironment to enhance IBC tumor growth. Changes in lymphatic structure and function were characterized with in vivo near-infrared fluorescence (NIRF) imaging. Mice were fed either a high-fat diet (HFD; 60 kcal%) or a normal/low-fat diet (LFD; 10 kcal%), bred twice, and subjected to either normal-duration nursing (NW) or forced weaning (FW). SUM149 IBC tumors were implanted at 14 months; images were obtained before and after implantation. Multiparous mice fed HFD showed increased pre-tumor lymphatic pulsing in both the FW and NW groups relative to mice fed LFD. HFD promoted tumor growth independent of weaning time (P = 0.04). Pre-tumor lymphatic pulsing was associated with tumor volume at 8 weeks (P = 0.02) and was significantly correlated with expression of the lymphatic tracking ligand CCL21 (P = 0.05, Table 1). HFD significantly increased the numbers of monocyte-derived IBA1⁺, CD163⁺, and CD11c⁺ cells (P < 0.0001, P < 0.0001, P = 0.0005) in the contralateral, non-tumor-bearing mammary gland. Numbers of lymphangiogenic podoplanin⁺/IBA1⁺ macrophages were increased in the ducts of HFD and FW mice (all P < 0.003). HFD in nulliparous mice had a similar increase in lymphatic pulsing at 14 weeks (P = 0.006), indicating that this functional change was independent of parity. We conclude that HFD induced increases in mammary gland lymphatic function, assessed as pulsing rate before tumor initiation, and correlated with inflammation in the mammary gland and increased SUM149 tumor growth. The relationship between diet, lymphatic pulsing, and tumor growth warrants further investigation.</p>","PeriodicalId":16413,"journal":{"name":"Journal of Mammary Gland Biology and Neoplasia","volume":"28 1","pages":"21"},"PeriodicalIF":2.5,"publicationDate":"2023-10-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10558390/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41157026","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"RETRACTED ARTICLE: Pure Primary Squamous Cell Carcinoma of the Breast Arising from the Epithelium of a Complex Mammary Cyst: A Case Report.","authors":"Deniz Tihan, Gülcin Hepgul, Meltem Kucukyilmaz, Mehmet Sar, Hakan Guven","doi":"10.1007/s10911-011-9208-2","DOIUrl":"10.1007/s10911-011-9208-2","url":null,"abstract":"","PeriodicalId":16413,"journal":{"name":"Journal of Mammary Gland Biology and Neoplasia","volume":"28 Suppl 1","pages":"23"},"PeriodicalIF":3.0,"publicationDate":"2023-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10384523","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Non-Linear Lymphatic Anatomy in Breast Cancer Patients Prior to Axillary Lymph Node Dissection: A Risk Factor For Lymphedema Development.","authors":"JacqueLyn R Kinney,&nbsp;Rosie Friedman,&nbsp;Erin Kim,&nbsp;Elizabeth Tillotson,&nbsp;Kathy Shillue,&nbsp;Bernard T Lee,&nbsp;Dhruv Singhal","doi":"10.1007/s10911-023-09545-x","DOIUrl":"https://doi.org/10.1007/s10911-023-09545-x","url":null,"abstract":"<p><p>Immediate lymphatic reconstruction (ILR) at the time of axillary lymph node dissection (ALND) has become increasingly utilized for the prevention of breast cancer related lymphedema. Preoperative indocyanine green (ICG) lymphography is routinely performed prior to an ILR procedure to characterize baseline lymphatic anatomy of the upper extremity. While most patients have linear lymphatic channels visualized on ICG, representing a non-diseased state, some patients demonstrate non-linear patterns. This study aims to determine potential inciting factors that help explain why some patients have non-linear patterns, and what these patterns represent regarding the relative risk of developing postoperative breast cancer related lymphedema in this population. A retrospective review was conducted to identify breast cancer patients who underwent successful ILR with preoperative ICG at our institution from November 2017-June 2022. Among the 248 patients who were identified, 13 (5%) had preoperative non-linear lymphatic anatomy. A history of trauma or surgery of the affected limb and an increasing number of sentinel lymph nodes removed prior to ALND appeared to be risk factors for non-linear lymphatic anatomy. Furthermore, non-linear anatomy in the limb of interest was associated with an increased risk of postoperative lymphedema development. Overall, non-linear lymphatic anatomy on pre-operative ICG lymphography appears to be a risk factor for developing ipsilateral breast cancer-related lymphedema. Guided by the study's findings, when breast cancer patients present with baseline non-linear lymphatic anatomy, our institution has implemented a protocol of prophylactically prescribing compression sleeves immediately following ALND.</p>","PeriodicalId":16413,"journal":{"name":"Journal of Mammary Gland Biology and Neoplasia","volume":"28 1","pages":"20"},"PeriodicalIF":2.5,"publicationDate":"2023-07-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10363047/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10220810","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Distinct Requirements for Adaptor Proteins NCK1 and NCK2 in Mammary Gland Development.","authors":"Adam P Golding,&nbsp;Benjamin Ferrier,&nbsp;Laura A New,&nbsp;Peihua Lu,&nbsp;Claire E Martin,&nbsp;Erka Shata,&nbsp;Robert A Jones,&nbsp;Roger A Moorehead,&nbsp;Nina Jones","doi":"10.1007/s10911-023-09541-1","DOIUrl":"https://doi.org/10.1007/s10911-023-09541-1","url":null,"abstract":"<p><p>The adaptor proteins NCK1 and NCK2 are well-established signalling nodes that regulate diverse biological processes including cell proliferation and actin dynamics in many tissue types. Here we have investigated the distribution and function of Nck1 and Nck2 in the developing mouse mammary gland. Using publicly available single-cell RNA sequencing data, we uncovered distinct expression profiles between the two paralogs. Nck1 showed widespread expression in luminal, basal, stromal and endothelial cells, while Nck2 was restricted to luminal and basal cells, with prominent enrichment in hormone-sensing luminal subtypes. Next, using mice with global knockout of Nck1 or Nck2, we assessed mammary gland development during and after puberty (5, 8 and 12 weeks of age). Mice lacking Nck1 or Nck2 displayed significant defects in ductal outgrowth and branching at 5 weeks compared to controls, and the defects persisted in Nck2 knockout mice at 8 weeks before normalizing at 12 weeks. These defects were accompanied by an increase in epithelial cell proliferation at 5 weeks and a decrease at 8 weeks in both Nck1 and Nck2 knockout mice. We also profiled expression of several key genes associated with mammary gland development at these timepoints and detected temporal changes in transcript levels of hormone receptors as well as effectors of cell proliferation and migration in Nck1 and Nck2 knockout mice, in line with the distinct phenotypes observed at 5 and 8 weeks. Together these studies reveal a requirement for NCK proteins in mammary gland morphogenesis, and suggest that deregulation of Nck expression could drive breast cancer progression and metastasis.</p>","PeriodicalId":16413,"journal":{"name":"Journal of Mammary Gland Biology and Neoplasia","volume":"28 1","pages":"19"},"PeriodicalIF":2.5,"publicationDate":"2023-07-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10361900/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9854036","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}