Alecia-Jane Twigger, Jakub Sumbal, Mohamed Bentires-Alj, Beatrice A Howard
{"title":"Thirteenth Annual ENBDC Workshop: Methods in Mammary Gland Biology and Breast Cancer.","authors":"Alecia-Jane Twigger, Jakub Sumbal, Mohamed Bentires-Alj, Beatrice A Howard","doi":"10.1007/s10911-022-09526-6","DOIUrl":"10.1007/s10911-022-09526-6","url":null,"abstract":"<p><p>The thirteenth annual workshop of the European Network for Breast Development and Cancer (ENBDC) Laboratories Annual Workshop took place on the 28-30 April 2022 in Weggis, Switzerland and focused on methods in mammary gland biology and breast cancer. Sixty scientists participated in the ENBDC annual workshop which had not been held in person since 2019 due to the global COVID-19 pandemic. Topics spanned the mammary gland biology field, ranging from lactation biology and embryonic development, single cell sequencing of the human breast, and stunning cutting-edge imaging of the mouse mammary gland and human breast as well as breast cancer research topics including invasive progression of the pre-invasive DCIS stage, metabolic determinants of endocrine therapy resistance, models for lobular breast cancer, and how mutational landscapes of normal breast during age and pregnancy determine cancer risk. The latest findings from participating researchers were presented through oral presentations and poster sessions and included plenty of unpublished work.</p>","PeriodicalId":16413,"journal":{"name":"Journal of Mammary Gland Biology and Neoplasia","volume":"27 3-4","pages":"233-239"},"PeriodicalIF":3.0,"publicationDate":"2022-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9568960/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10867312","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}
Eric P Souto, Lacey E Dobrolecki, Hugo Villanueva, Andrew G Sikora, Michael T Lewis
{"title":"In Vivo Modeling of Human Breast Cancer Using Cell Line and Patient-Derived Xenografts.","authors":"Eric P Souto, Lacey E Dobrolecki, Hugo Villanueva, Andrew G Sikora, Michael T Lewis","doi":"10.1007/s10911-022-09520-y","DOIUrl":"10.1007/s10911-022-09520-y","url":null,"abstract":"<p><p>Historically, human breast cancer has been modeled largely in vitro using long-established cell lines primarily in two-dimensional culture, but also in three-dimensional cultures of varying cellular and molecular complexities. A subset of cell line models has also been used in vivo as cell line-derived xenografts (CDX). While outstanding for conducting detailed molecular analysis of regulatory mechanisms that may function in vivo, results of drug response studies using long-established cell lines have largely failed to translate clinically. In an attempt to address this shortcoming, many laboratories have succeeded in developing clinically annotated patient-derived xenograft (PDX) models of human cancers, including breast, in a variety of host systems. While immunocompromised mice are the predominant host, the immunocompromised rat and pig, zebrafish, as well as the chicken egg chorioallantoic membrane (CAM) have also emerged as potential host platforms to help address perceived shortcomings of immunocompromised mice. With any modeling platform, the two main issues to be resolved are criteria for \"credentialing\" the models as valid models to represent human cancer, and utility with respect to the ability to generate clinically relevant translational research data. Such data are beginning to emerge, particularly with the activities of PDX consortia such as the NCI PDXNet Program, EuroPDX, and the International Breast Cancer Consortium, as well as a host of pharmaceutical companies and contract research organizations (CRO). This review focuses primarily on these important aspects of PDX-related research, with a focus on breast cancer.</p>","PeriodicalId":16413,"journal":{"name":"Journal of Mammary Gland Biology and Neoplasia","volume":"27 2","pages":"211-230"},"PeriodicalIF":3.0,"publicationDate":"2022-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9433358/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9548174","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":"Sodium Acetate and Sodium Butyrate Differentially Upregulate Antimicrobial Component Production in Mammary Glands of Lactating Goats","authors":"Yusaku Tsugami, Naoki Suzuki, T. Nii, N. Isobe","doi":"10.1007/s10911-022-09519-5","DOIUrl":"https://doi.org/10.1007/s10911-022-09519-5","url":null,"abstract":"","PeriodicalId":16413,"journal":{"name":"Journal of Mammary Gland Biology and Neoplasia","volume":"27 1","pages":"133 - 144"},"PeriodicalIF":2.5,"publicationDate":"2022-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"44050077","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}
Haruka Wakasa, Yusaku Tsugami, Taku Koyama, Liang Han, T. Nishimura, N. Isobe, Ken Kobayashi
{"title":"Adverse Effects of High Temperature On Mammary Alveolar Development In Vitro","authors":"Haruka Wakasa, Yusaku Tsugami, Taku Koyama, Liang Han, T. Nishimura, N. Isobe, Ken Kobayashi","doi":"10.1007/s10911-022-09518-6","DOIUrl":"https://doi.org/10.1007/s10911-022-09518-6","url":null,"abstract":"","PeriodicalId":16413,"journal":{"name":"Journal of Mammary Gland Biology and Neoplasia","volume":"27 1","pages":"155 - 170"},"PeriodicalIF":2.5,"publicationDate":"2022-05-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"43193401","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":"Circ_0008500 Knockdown Improves Radiosensitivity and Inhibits Tumorigenesis in Breast Cancer Through the miR-758-3p/PFN2 Axis.","authors":"Deyou Kong, Dongxing Shen, Zhikun Liu, Jun Zhang, Jian Zhang, Cuizhi Geng","doi":"10.1007/s10911-022-09514-w","DOIUrl":"10.1007/s10911-022-09514-w","url":null,"abstract":"<p><p>Breast cancer is one of the most common malignancies worldwide. Circular RNAs (CircRNAs) were revealed to be implicated in the development of breast cancer. In this research, we aimed to investigate the role and underlying mechanism of circ_0008500 in the development and radiosensitivity of breast cancer. Using real-time quantitative PCR (RT-qPCR) and western blot, we found that hsa_circ_0008500 (circ_0008500) and profilin 2 (PFN2) were increased, while microRNA-758-3p (miR-758-3p) was decreased in breast cancer tissues and cells. Cell viability, the number of colonies, proliferation and apoptosis were detected using CCK-8, colony formation, EdU assays and flow cytometry, respectively. Dual-luciferase reporter and RNA immunoprecipitation (RIP) assays were devoted to test the interaction between miR-758-3p and circ_0008500 or PFN2. The results showed that circ_0008500 knockdown inhibited cell growth, and facilitated cell apoptosis and radiosensitivity in breast cancer cells in vitro. Moreover, circ_0008500 regulated PFN2 expression by sponging miR-758-3p. Functionally, circ_0008500 knockdown regulated cell behaviors and radiosensitivity by targeting miR-758-3p to downregulate PFN2 expression in vitro. Additionally, in vivo tumor formation assay and immunohistochemistry (IHC) assay demonstrated that circ_0008500 knockdown enhanced the radiosensitivity and repressed tumor growth in vivo. In conclusion, circ_0008500 inhibition promoted the radiosensitivity and restrained the development of breast cancer by downregulating PFN2 expression via targeting miR-758-3p.</p>","PeriodicalId":16413,"journal":{"name":"Journal of Mammary Gland Biology and Neoplasia","volume":"27 1","pages":"37-52"},"PeriodicalIF":2.5,"publicationDate":"2022-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41359950","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}
Zach Carlson, Hannah Hafner, Noura El Habbal, Emma Harman, Stephanie Liu, Nathalie Botezatu, Masa Alharastani, Cecilia Rivet, Holly Reynolds, Nyahon Both, Haijing Sun, Dave Bridges, Brigid Gregg
{"title":"Short Term Changes in Dietary Fat Content and Metformin Treatment During Lactation Impact Milk Composition and Mammary Gland Morphology.","authors":"Zach Carlson, Hannah Hafner, Noura El Habbal, Emma Harman, Stephanie Liu, Nathalie Botezatu, Masa Alharastani, Cecilia Rivet, Holly Reynolds, Nyahon Both, Haijing Sun, Dave Bridges, Brigid Gregg","doi":"10.1007/s10911-022-09512-y","DOIUrl":"10.1007/s10911-022-09512-y","url":null,"abstract":"<p><p>Maternal health and diet can have important consequences for offspring nutrition and metabolic health. During lactation, signals are communicated from the mother to the infant through milk via macronutrients, hormones, and bioactive molecules. In this study we designed experiments to probe the mother-milk-infant triad in the condition of normal maternal health and upon exposure to high fat diet (HFD) with or without concurrent metformin exposure. We examined maternal characteristics, milk composition and offspring metabolic parameters on postnatal day 16, prior to offspring weaning. We found that lactational HFD increased maternal adipose tissue weight, mammary gland adipocyte size, and altered milk lipid composition causing a higher amount of omega-6 (n6) long chain fatty acids and lower omega-3 (n3). Offspring of HFD dams were heavier with more body fat during suckling. Metformin (Met) exposure decreased maternal blood glucose and several milk amino acids. Offspring of met dams were smaller during suckling. Gene expression in the lactating mammary glands was impacted to a greater extent by metformin than HFD, but both metformin and HFD altered genes related to muscle contraction, indicating that these genes may be more susceptible to lactational stressors. Our study demonstrates the impact of common maternal exposures during lactation on milk composition, mammary gland function and offspring growth with metformin having little capacity to rescue the offspring from the effects of a maternal HFD during lactation.</p>","PeriodicalId":16413,"journal":{"name":"Journal of Mammary Gland Biology and Neoplasia","volume":"27 1","pages":"1-18"},"PeriodicalIF":2.5,"publicationDate":"2022-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9383157","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}
Marit Valla, Elise Klæstad, Borgny Ytterhus, Anna M Bofin
{"title":"CCND1 Amplification in Breast Cancer -associations With Proliferation, Histopathological Grade, Molecular Subtype and Prognosis.","authors":"Marit Valla, Elise Klæstad, Borgny Ytterhus, Anna M Bofin","doi":"10.1007/s10911-022-09516-8","DOIUrl":"10.1007/s10911-022-09516-8","url":null,"abstract":"<p><p>CCND1 is located on 11q13. Increased CCND1 copy number (CN) in breast cancer (BC) is associated with high histopathological grade, high proliferation, and Luminal B subtype. In this study of CCND1 in primary BCs and corresponding axillary lymph node metastases (LNM),we examine associations between CCND1 CN in primary BCs and proliferation status, molecular subtype, and prognosis. Furthermore, we studied associations between CCND1 CN and CNs of FGFR1 and ZNF703, both of which are located on 8p12. Fluorescence in situ hybridization probes for CCND1 and chromosome 11 centromere were used on tissue microarrays comprising 526 BCs and 123 LNM. We assessed associations between CCND1 CN and tumour characteristics using Pearson's χ<sup>2</sup> test, and estimated cumulative risks of death from BC and hazard ratios in analysis of prognosis. We found CCND1 CN ≥ 4 < 6 in 45 (8.6%) tumours, and ≥ 6 in 42 (8.0%). CCND1 CN (≥ 6) was seen in all molecular subtypes, most frequently in Luminal B (HER2<sup>-</sup>) (20/126; 16%). Increased CCND1 CN was associated with high histopathological grade, high Ki-67, and high mitotic count, but not prognosis. CCND1 CN ≥ 6 was accompanied by CN increase of FGFR1 in 6/40 cases (15.0%) and ZNF703 in 5/38 cases (13.2%). Three cases showed CN increase of all three genes. High CCND1 CN was most frequent in Luminal B (HER2<sup>-</sup>) tumours. Good correlation between CCND1 CNs in BCs and LNM was observed. Despite associations between high CCND1 CN and aggressive tumour characteristics, the prognostic impact of CCND1 CN remains unresolved.</p>","PeriodicalId":16413,"journal":{"name":"Journal of Mammary Gland Biology and Neoplasia","volume":"27 1","pages":"67-77"},"PeriodicalIF":2.5,"publicationDate":"2022-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9135839/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"46851350","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}
Gemma M Wilson, Phuong Dinh, Nirmala Pathmanathan, J Dinny Graham
{"title":"Ductal Carcinoma in Situ: Molecular Changes Accompanying Disease Progression.","authors":"Gemma M Wilson, Phuong Dinh, Nirmala Pathmanathan, J Dinny Graham","doi":"10.1007/s10911-022-09517-7","DOIUrl":"10.1007/s10911-022-09517-7","url":null,"abstract":"<p><p>Ductal carcinoma in situ (DCIS) is a non-obligate precursor of invasive ductal carcinoma (IDC), whereby if left untreated, approximately 12% of patients develop invasive disease. The current standard of care is surgical removal of the lesion, to prevent potential progression, and radiotherapy to reduce risk of recurrence. There is substantial overtreatment of DCIS patients, considering not all DCIS lesions progress to invasive disease. Hence, there is a critical imperative to better predict which DCIS lesions are destined for poor outcome and which are not, allowing for tailored treatment. Active surveillance is currently being trialed as an alternative management practice, but this approach relies on accurately identifying cases that are at low risk of progression to invasive disease. Two DCIS-specific genomic profiling assays that attempt to distinguish low and high-risk patients have emerged, but imperfections in risk stratification coupled with a high price tag warrant the continued search for more robust and accessible prognostic biomarkers. This search has largely turned researchers toward the tumor microenvironment. Recent evidence suggests that a spectrum of cell types within the DCIS microenvironment are genetically and phenotypically altered compared to normal tissue and play critical roles in disease progression. Uncovering the molecular mechanisms contributing to DCIS progression has provided optimism for the search for well-validated prognostic biomarkers that can accurately predict the risk for a patient developing IDC. The discovery of such markers would modernize DCIS management and allow tailored treatment plans. This review will summarize the current literature regarding DCIS diagnosis, treatment, and pathology.</p>","PeriodicalId":16413,"journal":{"name":"Journal of Mammary Gland Biology and Neoplasia","volume":"27 1","pages":"101-131"},"PeriodicalIF":2.5,"publicationDate":"2022-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9135892/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"44034466","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":"Altered Epithelial-mesenchymal Plasticity as a Result of Ovol2 Deletion Minimally Impacts the Self-renewal of Adult Mammary Basal Epithelial Cells.","authors":"Peng Sun, Yingying Han, Maksim Plikus, Xing Dai","doi":"10.1007/s10911-021-09508-0","DOIUrl":"10.1007/s10911-021-09508-0","url":null,"abstract":"<p><p>Stem-cell containing mammary basal epithelial cells exist in a quasi-mesenchymal transcriptional state characterized by simultaneous expression of typical epithelial genes and typical mesenchymal genes. Whether robust maintenance of such a transcriptional state is required for adult basal stem cells to fuel self-renewal and regeneration remains unclear. In this work, we utilized SMA-CreER to direct efficient basal cell-specific deletion of Ovol2, which encodes a transcription factor that inhibits epithelial-to-mesenchymal transition (EMT), in adult mammary gland. We identified a basal cell-intrinsic role of Ovol2 in promoting epithelial, and suppressing mesenchymal, molecular traits. Interestingly, Ovol2-deficient basal cells display minimal perturbations in their ability to support tissue homeostasis, colony formation, and transplant outgrowth. These findings underscore the ability of adult mammary basal cells to tolerate molecular perturbations associated with altered epithelia-mesenchymal plasticity without drastically compromising their self-renewal potential.</p>","PeriodicalId":16413,"journal":{"name":"Journal of Mammary Gland Biology and Neoplasia","volume":"26 4","pages":"377-386"},"PeriodicalIF":3.0,"publicationDate":"2021-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8858298/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9248730","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}
Weizhen Chen, Wei Wei, Liya Yu, Zi Ye, Fujing Huang, Liyan Zhang, Shiqi Hu, Cheguo Cai
{"title":"Mammary Development and Breast Cancer: a Notch Perspective.","authors":"Weizhen Chen, Wei Wei, Liya Yu, Zi Ye, Fujing Huang, Liyan Zhang, Shiqi Hu, Cheguo Cai","doi":"10.1007/s10911-021-09496-1","DOIUrl":"https://doi.org/10.1007/s10911-021-09496-1","url":null,"abstract":"<p><p>Mammary gland development primarily occurs postnatally, and this unique process is complex and regulated by systemic hormones and local growth factors. The mammary gland is also a highly dynamic organ that undergoes profound changes at puberty and during the reproductive cycle. These changes are driven by mammary stem cells (MaSCs). Breast cancer is one of the most common causes of cancer-related death in women. Cancer stem cells (CSCs) play prominent roles in tumor initiation, drug resistance, tumor recurrence, and metastasis. The highly conserved Notch signaling pathway functions as a key regulator of the niche mediating mammary organogenesis and breast neoplasia. In this review, we discuss mechanisms by which Notch contributes to breast carcinoma pathology and suggest potentials for therapeutic targeting of Notch in breast cancer. In summary, we provide a comprehensive overview of Notch functions in regulating MaSCs, mammary development, and breast cancer.</p>","PeriodicalId":16413,"journal":{"name":"Journal of Mammary Gland Biology and Neoplasia","volume":"26 3","pages":"309-320"},"PeriodicalIF":2.5,"publicationDate":"2021-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1007/s10911-021-09496-1","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39297513","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}