Journal of Mammary Gland Biology and Neoplasia最新文献

{"title":"Changes in Immune Cell Types with Age in Breast are Consistent with a Decline in Immune Surveillance and Increased Immunosuppression.","authors":"Arrianna Zirbes,&nbsp;Jesuchristopher Joseph,&nbsp;Jennifer C Lopez,&nbsp;Rosalyn W Sayaman,&nbsp;Mudaser Basam,&nbsp;Victoria L Seewaldt,&nbsp;Mark A LaBarge","doi":"10.1007/s10911-021-09495-2","DOIUrl":"https://doi.org/10.1007/s10911-021-09495-2","url":null,"abstract":"<p><p>A majority of breast cancers (BC) are age-related and we seek to determine what cellular and molecular changes occur in breast tissue with age that make women more susceptible to cancer initiation. Immune-epithelial cell interactions are important during mammary gland development and the immune system plays an important role in BC progression. The composition of human immune cell populations is known to change in peripheral blood with age and in breast tissue during BC progression. Less is known about changes in immune populations in normal breast tissue and how their interactions with mammary epithelia change with age. We quantified densities of T cells, B cells, and macrophage subsets in pathologically normal breast tissue from 122 different women who ranged in age from 24 to 74 years old. Donor-matched peripheral blood from a subset of 20 donors was analyzed by flow cytometry. Tissue immune cell densities and localizations relative to the epithelium were quantified in situ with machine learning-based image analyses of multiplex immunohistochemistry-stained tissue sections. In situ results were corroborated with flow cytometry analyses of peri-epithelial immune cells from primary breast tissue preparations and transcriptome analyses of public data from bulk tissue reduction mammoplasties. Proportions of immune cell subsets in breast tissue and donor-matched peripheral blood were not correlated. Density (cells/mm²) of T and B lymphocytes in situ decreased with age. T cells and macrophages preferentially localized near or within epithelial bilayers, rather than the intralobular stroma. M2 macrophage density was higher than M1 macrophage density and this difference was due to higher density of M2 in the intralobular stroma. Transcriptional signature analyses suggested age-dependent decline in adaptive immune cell populations and functions and increased innate immune cell activity. T cells and macrophages are so intimately associated with the epithelia that they are embedded within the bilayer, suggesting an important role for immune-epithelial cell interactions. Age-associated decreased T cell density in peri-epithelial regions, and increased M2 macrophage density in intralobular stroma suggests the emergence of a tissue microenvironment that is simultaneously immune-senescent and immunosuppressive with age.</p>","PeriodicalId":16413,"journal":{"name":"Journal of Mammary Gland Biology and Neoplasia","volume":"26 3","pages":"247-261"},"PeriodicalIF":2.5,"publicationDate":"2021-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8566425/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39272024","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":"Mechanical Pressure Driving Proteoglycan Expression in Mammographic Density: a Self-perpetuating Cycle?","authors":"Gina Reye,&nbsp;Xuan Huang,&nbsp;Larisa M Haupt,&nbsp;Ryan J Murphy,&nbsp;Jason J Northey,&nbsp;Erik W Thompson,&nbsp;Konstantin I Momot,&nbsp;Honor J Hugo","doi":"10.1007/s10911-021-09494-3","DOIUrl":"https://doi.org/10.1007/s10911-021-09494-3","url":null,"abstract":"<p><p>Regions of high mammographic density (MD) in the breast are characterised by a proteoglycan (PG)-rich fibrous stroma, where PGs mediate aligned collagen fibrils to control tissue stiffness and hence the response to mechanical forces. Literature is accumulating to support the notion that mechanical stiffness may drive PG synthesis in the breast contributing to MD. We review emerging patterns in MD and other biological settings, of a positive feedback cycle of force promoting PG synthesis, such as in articular cartilage, due to increased pressure on weight bearing joints. Furthermore, we present evidence to suggest a pro-tumorigenic effect of increased mechanical force on epithelial cells in contexts where PG-mediated, aligned collagen fibrous tissue abounds, with implications for breast cancer development attributable to high MD. Finally, we summarise means through which this positive feedback mechanism of PG synthesis may be intercepted to reduce mechanical force within tissues and thus reduce disease burden.</p>","PeriodicalId":16413,"journal":{"name":"Journal of Mammary Gland Biology and Neoplasia","volume":"26 3","pages":"277-296"},"PeriodicalIF":2.5,"publicationDate":"2021-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1007/s10911-021-09494-3","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39358203","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":"In Utero Exposure to trans-10, cis-12 Conjugated Linoleic Acid Modifies Postnatal Development of the Mammary Gland and its Hormone Responsiveness.","authors":"Grace E Berryhill,&nbsp;Julia M Gloviczki,&nbsp;Josephine F Trott,&nbsp;Jana Kraft,&nbsp;Adam L Lock,&nbsp;Russell C Hovey","doi":"10.1007/s10911-021-09499-y","DOIUrl":"https://doi.org/10.1007/s10911-021-09499-y","url":null,"abstract":"<p><p>We previously showed that dietary trans-10, cis-12 conjugated linoleic acid (10,12 CLA) stimulates estrogen-independent mammary growth in young ovariectomized mice. Here we investigated the effects of in utero or postnatal exposure to cis-9, trans-11 (9,11 CLA) and 10,12 CLA on postnatal development of the mammary gland and its responsiveness to ovarian steroids. In the first experiment we fed dams different CLA prior to and during gestation, then cross fostered female pups onto control fed dams prior to assessing the histomorphology of their mammary glands. Pregnant dams in the second experiment were similarly exposed to CLA, after which their female pups were ovariectomized then treated with 17β-estradiol (E), progesterone (P) or E + P for 5 days. In a third experiment, mature female mice were fed different CLA for 28 days prior to ovariectomy, then treated with E, P or E + P. Our data indicate that 10,12 CLA modifies the responsiveness of the mammary glands to E or E + P when exposure occurs either in utero, or postnatally. These findings underline the sensitivity of the mammary glands to dietary fatty acids and reinforce the potential for maternal nutrition to impact postnatal development of the mammary glands and their risk for developing cancer.</p>","PeriodicalId":16413,"journal":{"name":"Journal of Mammary Gland Biology and Neoplasia","volume":"26 3","pages":"263-276"},"PeriodicalIF":2.5,"publicationDate":"2021-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8566432/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39492517","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":"Interactions of BRCA1-mutated Breast Cancer Cell Lines with Adipose-derived Stromal Cells (ADSCs).","authors":"Adelina Plangger,&nbsp;Werner Haslik,&nbsp;Barbara Rath,&nbsp;Christoph Neumayer,&nbsp;Gerhard Hamilton","doi":"10.1007/s10911-021-09493-4","DOIUrl":"https://doi.org/10.1007/s10911-021-09493-4","url":null,"abstract":"<p><p>Lipofilling may constitute a technique to assist reconstruction of breasts following prophylactic mastectomy for patients with mutated BRCA1 or BRCA2 genes. However, to date it is not clear whether adipose-derived stromal cells (ADSCs) increase the risk of tumor initiation and progression in this situation. Therefore, the interactions of BRCA1 mutated breast cancer cell lines with normal ADSCs were investigated in the present study. Characteristics of MDA-MB-436 (BRCA1 c.5277 + 1G > A) and HCC1937 (BRCA1 p.Gln1756.Profs*74) were compared to MDA-MB-231 and T47D BRCA1/2 wild-type breast cancer cell lines. ADSCs were cultivated from lipoaspirates of a panel of BRCA1/2- wildtype patients. Interactions of conditioned medium (CM) of these cells with the breast cancer lines were studied using proliferation and migration assays as well as adipokine expression western blot arrays. CM of ADSCs exhibit a dose-dependent stimulation of the proliferation of the breast cancer cell lines. However, of the ADSC preparations tested, only 1 out of 18 samples showed a significant higher stimulation of BRCA1-mutated MDA-MB-436 versus wildtype MDA-MB-231 cells, and all CM revealed lower stimulatory activity for BRCA1-mutated HCC1937 versus wildtype T47D cells. Additionally, migration of breast cancer cells in response to CM of ADSCs proved to be equivalent or slower for BRCA1/2 mutated versus nonmutated cancer cells and, with exception of angiopoietin-like 2, induced expression of adipokines showed no major difference. Effects of media conditioned by normal ADSCs showed largely comparable effects on BRCA1-mutated and wildtype breast cancer cell lines thus advocating lipofilling, preferentially employing allogeneic non-mutated ADSCs.</p>","PeriodicalId":16413,"journal":{"name":"Journal of Mammary Gland Biology and Neoplasia","volume":"26 3","pages":"235-245"},"PeriodicalIF":2.5,"publicationDate":"2021-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1007/s10911-021-09493-4","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39154930","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":"The BA-BCS 2021: An Initial \"Trial\" for Integrating Basic Science and Medical Progress on Breast Cancer in a Latin-American Country.","authors":"Edith Kordon,&nbsp;Claudia Lanari,&nbsp;Pablo Mando,&nbsp;Virginia Novaro,&nbsp;Mario Rossi,&nbsp;Marina Simian","doi":"10.1007/s10911-021-09501-7","DOIUrl":"https://doi.org/10.1007/s10911-021-09501-7","url":null,"abstract":"<p><p>The first Buenos Aires Breast Cancer Symposium (BA-BCS) was held in a virtual format, between the 17^th and the 21^st of May 2021. The main goal of the meeting was to facilitate the interaction among physicians and basic researchers from South America and with peers from the rest of the world. To embrace their different interests and concerns, the congress included not only talks on basic, translational and clinical research, but also round tables to discuss diagnostic methods, research financing and biobank management, as well as virtual poster sessions in which the youngest fellows presented their recent findings. This report provides a brief overview of the talks delivered during the meeting, which addressed a wide variety of vital issues for breast cancer research mostly focused on the accurate diagnosis, prevention and treatment of this illness. The presentations included a wide spectrum of themes including hormone receptors and the relevance of their mutations, immunotherapy, cancer stem cells, mouse models, environmental hazards, genetics and epigenetics, local and systemic therapies, liquid biopsies, the metastatic cascade, therapy resistance and dormancy, among others.</p>","PeriodicalId":16413,"journal":{"name":"Journal of Mammary Gland Biology and Neoplasia","volume":"26 3","pages":"227-234"},"PeriodicalIF":2.5,"publicationDate":"2021-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8510571/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39515580","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":"Evolution and Self-renewal of the Journal of Mammary Gland Biology and Neoplasia.","authors":"Russell C Hovey, Zuzana Koledova","doi":"10.1007/s10911-021-09500-8","DOIUrl":"10.1007/s10911-021-09500-8","url":null,"abstract":"","PeriodicalId":16413,"journal":{"name":"Journal of Mammary Gland Biology and Neoplasia","volume":"26 3","pages":"217-220"},"PeriodicalIF":3.0,"publicationDate":"2021-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8515151/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39517013","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":"Twelfth Annual ENBDC Workshop: Methods in Mammary Gland Biology and Breast Cancer.","authors":"Elsa Charifou, Gunnhildur Asta Traustadottir, Mohamed Bentires-Alj, Beatrice Howard, Alexandra Van Keymeulen","doi":"10.1007/s10911-021-09498-z","DOIUrl":"10.1007/s10911-021-09498-z","url":null,"abstract":"<p><p>The twelfth annual workshop of the European Network for Breast Development and Cancer focused on methods in mammary gland biology and breast cancer, was scheduled to take place on March 26-28, 2020, in Weggis, Switzerland. Due to the COVID-19 pandemic, the meeting was rescheduled twice and eventually happened as a virtual meeting on April 22 and 23, 2021. The main topics of the meeting were branching and development of the mammary gland, tumor microenvironment, circulating tumor cells, tumor dormancy and breast cancer metastasis. Novel and unpublished findings related to these topics were presented, with a particular focus on the methods used to obtain them. Virtual poster sessions were a success, with many constructive and fruitful interactions between researchers and covered many areas of mammary gland biology and breast cancer.</p>","PeriodicalId":16413,"journal":{"name":"Journal of Mammary Gland Biology and Neoplasia","volume":"26 3","pages":"221-226"},"PeriodicalIF":2.5,"publicationDate":"2021-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8390087/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39357376","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":"Estetrol and Mammary Gland: Friends or Foes?","authors":"Anne Gallez,&nbsp;Isabelle Dias Da Silva,&nbsp;Vincent Wuidar,&nbsp;Jean-Michel Foidart,&nbsp;Christel Péqueux","doi":"10.1007/s10911-021-09497-0","DOIUrl":"https://doi.org/10.1007/s10911-021-09497-0","url":null,"abstract":"<p><p>Estrogens have pleiotropic effects on many reproductive and non-reproductive tissues and organs including the mammary gland, uterus, ovaries, vagina, and endothelium. Estrogen receptor α functions as the principal mediator of estrogenic action in most of these tissues. Estetrol (E4) is a native fetal estrogen with selective tissue actions that is currently approved for use as the estrogen component in a combined oral contraceptive and is being developed as a menopause hormone therapy (MHT, also known as hormone replacement therapy). However, exogenous hormonal treatments, in particular MHTs, have been shown to promote the growth of preexisting breast cancers and are associated with a variable risk of breast cancer depending on the treatment modality. Therefore, evaluating the safety of E4-based formulations on the breast forms a crucial part of the clinical development process. This review highlights preclinical and clinical studies that have assessed the effects of E4 and E4-progestogen combinations on the mammary gland and breast cancer, focusing in particular on the estrogenic and anti-estrogenic properties of E4. We discuss the potential advantages of E4 over current available estrogen-formulations as a contraceptive and for the treatment of symptoms due to menopause. We also consider the potential of E4 for the treatment of endocrine-resistant breast cancer.</p>","PeriodicalId":16413,"journal":{"name":"Journal of Mammary Gland Biology and Neoplasia","volume":"26 3","pages":"297-308"},"PeriodicalIF":2.5,"publicationDate":"2021-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8566418/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39369690","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":"Epithelial p53 Status Modifies Stromal-Epithelial Interactions During Basal-Like Breast Carcinogenesis.","authors":"Ashley M Fuller,&nbsp;Lin Yang,&nbsp;Alina M Hamilton,&nbsp;Jason R Pirone,&nbsp;Amy L Oldenburg,&nbsp;Melissa A Troester","doi":"10.1007/s10911-020-09477-w","DOIUrl":"https://doi.org/10.1007/s10911-020-09477-w","url":null,"abstract":"<p><p>Basal-like breast cancers (BBC) exhibit subtype-specific phenotypic and transcriptional responses to stroma, but little research has addressed how stromal-epithelial interactions evolve during early BBC carcinogenesis. It is also unclear how common genetic defects, such as p53 mutations, modify these stromal-epithelial interactions. To address these knowledge gaps, we leveraged the MCF10 progression series of breast cell lines (MCF10A, MCF10AT1, and MCF10DCIS) to develop a longitudinal, tissue-contextualized model of p53-deficient, pre-malignant breast. Acinus asphericity, a morphogenetic correlate of cell invasive potential, was quantified with optical coherence tomography imaging, and gene expression microarrays were performed to identify transcriptional changes associated with p53 depletion and stromal context. Co-culture with stromal fibroblasts significantly increased the asphericity of acini derived from all three p53-deficient, but not p53-sufficient, cell lines, and was associated with the upregulation of 38 genes. When considered as a multigene score, these genes were upregulated in co-culture models of invasive BBC with increasing stromal content, as well as in basal-like relative to luminal breast cancers in two large human datasets. Taken together, stromal-epithelial interactions during early BBC carcinogenesis are dependent upon epithelial p53 status, and may play important roles in the acquisition of an invasive morphologic phenotype.</p>","PeriodicalId":16413,"journal":{"name":"Journal of Mammary Gland Biology and Neoplasia","volume":"26 2","pages":"89-99"},"PeriodicalIF":2.5,"publicationDate":"2021-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1007/s10911-020-09477-w","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38814464","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 Comparative Review of the Cell Biology, Biochemistry, and Genetics of Lactose Synthesis.","authors":"Anna Sadovnikova,&nbsp;Sergio C Garcia,&nbsp;Russell C Hovey","doi":"10.1007/s10911-021-09490-7","DOIUrl":"https://doi.org/10.1007/s10911-021-09490-7","url":null,"abstract":"<p><p>Lactose is the primary carbohydrate in the milk of most mammals and is unique in that it is only synthesized by epithelial cells in the mammary glands. Lactose is also essential for the development and nutrition of infants. Across species, the concentration of lactose in milk holds a strong positive correlation with overall milk volume. Additionally, there is a range of examples where the onset of lactose synthesis as well as the content of lactose in milk varies between species and throughout a lactation. Despite this diversity, the precursors, genes, proteins and ions that regulate lactose synthesis have not received the depth of study they likely deserve relative to the significance of this simple and abundant molecule. Through this review, our objective is to highlight the requirements for lactose synthesis at the biochemical, cellular and temporal levels through a comparative approach. This overview also serves as the prelude to a companion review describing the dietary, hormonal, molecular, and genetic factors that regulate lactose synthesis.</p>","PeriodicalId":16413,"journal":{"name":"Journal of Mammary Gland Biology and Neoplasia","volume":"26 2","pages":"181-196"},"PeriodicalIF":2.5,"publicationDate":"2021-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1007/s10911-021-09490-7","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39024558","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}