Journal of Mammary Gland Biology and Neoplasia最新文献

{"title":"Chloroquine Induces ROS-mediated Macrophage Migration Inhibitory Factor Secretion and Epithelial to Mesenchymal Transition in ER-positive Breast Cancer Cell Lines.","authors":"Guadalupe Rojas-Sanchez,&nbsp;Alin García-Miranda,&nbsp;José Benito Montes-Alvarado,&nbsp;Israel Cotzomi-Ortega,&nbsp;Fabiola Lilí Sarmiento-Salinas,&nbsp;Eduardo Eleazar Jimenez-Ignacio,&nbsp;Dalia Ramírez-Ramírez,&nbsp;Rubí Esmeralda Romo-Rodríguez,&nbsp;Julio Reyes-Leyva,&nbsp;Verónica Vallejo-Ruiz,&nbsp;Nidia Gary Pazos-Salazar,&nbsp;Paola Maycotte","doi":"10.1007/s10911-021-09503-5","DOIUrl":"https://doi.org/10.1007/s10911-021-09503-5","url":null,"abstract":"<p><p>Breast cancer (BC) is the leading cause of cancer-related death in women in the world. Since tumor cells employ autophagy as a survival pathway, it has been proposed that autophagy inhibition could be beneficial for cancer treatment. There are several onging clinical trials where autophagy is being inhibited (using chloroquine, CQ or hydroxychloroquine, HCQ) along with chemotherapy with promising results. However, there is also in vitro evidence in which autophagy inhibition can induce epithelial to mesenchymal transition (EMT) in cancer cells, indicating that, at least in some cases, this strategy could be detrimental for cancer patients. In this study, we found that the genetic inhibition of autophagy primed cells for EMT by inducing a decrease in E-cadherin protein levels, while CQ treatment decreased E-cadherin levels, induced morphological changes related to EMT, increased EMT-related transcription factor (EMT-TF) expression and migration in estrogen receptor positive (ER +) BC cell lines. Importantly, CQ treatment increased intracellular reactive oxygen species (ROS) which induced the secretion of macrophage migration inhibitory factor (MIF), a pro-inflammatory cytokine related to malignancy. Both ROS production and MIF secretion were responsible for the mesenchymal morphology and increased migratory capacity induced by CQ. Our results indicate that CQ treatment increased malignancy by inducing ROS production, MIF secretion and EMT and suggest that autophagy inhibition in ER + BC patients might have detrimental effects. Our data indicates that a careful selection of patients should be performed in order to determine who will benefit the most from autophagy inhibition with available pharmacological agents for the treatment of breast cancer.</p>","PeriodicalId":16413,"journal":{"name":"Journal of Mammary Gland Biology and Neoplasia","volume":" ","pages":"341-355"},"PeriodicalIF":2.5,"publicationDate":"2021-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39903994","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":"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}

{"title":"Stromal Changes are Associated with High P4HA2 Expression in Ductal Carcinoma in Situ of the Breast.","authors":"Marie Colombe Agahozo,&nbsp;Mieke van Bockstal,&nbsp;Pieter J Westenend,&nbsp;Christine Galant,&nbsp;Kathleen Lambein,&nbsp;Emily Reisenbichler,&nbsp;Renata Sinke,&nbsp;Serena Wong,&nbsp;Carolien H M van Deurzen","doi":"10.1007/s10911-021-09504-4","DOIUrl":"https://doi.org/10.1007/s10911-021-09504-4","url":null,"abstract":"<p><p>Ductal carcinoma in situ (DCIS) of the breast is able to induce stromal changes, which likely reflect the crosstalk between DCIS and its microenvironment. These changes harbor prognostic information, although the interobserver variability of scoring stromal changes is moderate. A more robust evaluation of the DCIS-associated stroma is therefore needed. The aim of this study was to characterize P4HA2 expression, which is involved in collagen biosynthesis, in DCIS and to assess whether P4HA2 expression enables a more robust evaluation of the DCIS-associated stroma compared to histomorphology. This study included 410 patients with DCIS. Stromal changes were scored on hematoxylin/eosin-stained whole slides. P4HA2 expression in DCIS-associated stroma was assessed by whole slide immunohistochemistry. One hundred DCIS lesions were evaluated by seven pathologists to study the interobserver variability in the assessment of stromal changes and stromal P4HA2 expression. High P4HA2 expression in stromal fibroblasts was present in 14.1% of the patients. High P4HA2 expression was associated with the presence of periductal stromal changes (P = 0.004). The interobserver variability was similar for the assessment of stromal changes and the percentage of P4HA2-positive fibroblasts. Although we demonstrated a significant association between high P4HA2 expression in fibroblasts and the morphological presence of stromal changes, it seems unlikely that P4HA2 expression can be used as an alternative for the histopathological evaluation of the DCIS-associated stroma.</p>","PeriodicalId":16413,"journal":{"name":"Journal of Mammary Gland Biology and Neoplasia","volume":" ","pages":"367-375"},"PeriodicalIF":2.5,"publicationDate":"2021-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8858280/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39857740","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":"Correction to: Peroxidasin Enhances Basal Phenotype and Inhibits Branching Morphogenesis in Breast Epithelial Progenitor Cell Line D492.","authors":"Anna Karen Sigurdardottir,&nbsp;Arna Steinunn Jonasdottir,&nbsp;Arni Asbjarnarson,&nbsp;Hildur Run Helgudottir,&nbsp;Thorarinn Gudjonsson,&nbsp;Gunnhildur Asta Traustadottir","doi":"10.1007/s10911-022-09513-x","DOIUrl":"https://doi.org/10.1007/s10911-022-09513-x","url":null,"abstract":"","PeriodicalId":16413,"journal":{"name":"Journal of Mammary Gland Biology and Neoplasia","volume":" ","pages":"339"},"PeriodicalIF":2.5,"publicationDate":"2021-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8858265/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39608218","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":"Advances in Analyzing the Breast Cancer Lipidome and Its Relevance to Disease Progression and Treatment.","authors":"Ashley V Ward,&nbsp;Steven M Anderson,&nbsp;Carol A Sartorius","doi":"10.1007/s10911-021-09505-3","DOIUrl":"https://doi.org/10.1007/s10911-021-09505-3","url":null,"abstract":"<p><p>Abnormal lipid metabolism is common in breast cancer with the three main subtypes, hormone receptor (HR) positive, human epidermal growth factor 2 (HER2) positive, and triple negative, showing common and distinct lipid dependencies. A growing body of studies identify altered lipid metabolism as impacting breast cancer cell growth and survival, plasticity, drug resistance, and metastasis. Lipids are a class of nonpolar or polar (amphipathic) biomolecules that can be produced in cells via de novo synthesis or acquired from the microenvironment. The three main functions of cellular lipids are as essential components of membranes, signaling molecules, and nutrient storage. The use of mass spectrometry-based lipidomics to analyze the global cellular lipidome has become more prevalent in breast cancer research. In this review, we discuss current lipidomic methodologies, highlight recent breast cancer lipidomic studies and how these findings connect to disease progression and therapeutic development, and the potential use of lipidomics as a diagnostic tool in breast cancer. A better understanding of the breast cancer lipidome and how it changes during drug resistance and tumor progression will allow informed development of diagnostics and novel targeted therapies.</p>","PeriodicalId":16413,"journal":{"name":"Journal of Mammary Gland Biology and Neoplasia","volume":" ","pages":"399-417"},"PeriodicalIF":2.5,"publicationDate":"2021-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8883833/pdf/nihms-1776602.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39730131","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":"Colostrogenesis: Role and Mechanism of the Bovine Fc Receptor of the Neonate (FcRn).","authors":"Craig R Baumrucker,&nbsp;Ann L Macrina,&nbsp;Rupert M Bruckmaier","doi":"10.1007/s10911-021-09506-2","DOIUrl":"https://doi.org/10.1007/s10911-021-09506-2","url":null,"abstract":"<p><p>Colostrogenesis is a separate and unique phase of mammary epithelial cell activity occurring in the weeks before parturition and rather abruptly ending after birth in the bovine. It has been the focus of research to define what controls this process and how it produces high concentrations of specific biologically active components important for the neonate. In this review we consider colostrum composition and focus upon components that appear in first milked colostrum in concentrations exceeding that in blood serum. The Fc Receptor of the Neonate (FcRn) is recognized as the major immunoglobulin G (IgG) and albumin binding protein that accounts for the proteins' long half-lives. We integrate the action of the pinocytotic (fluid phase) uptake of extracellular components and merge them with FcRn in sorting endosomes. We define and explore the means of binding, sorting, and the transcytotic delivery of IgG1 while recycling IgG2 and albumin. We consider the means of releasing the ligands from the receptor within the endosome and describe a new secretion mechanism of cargo release into colostrum without the appearance of FcRn itself in colostrum. We integrate the insulin-like growth factor family, some of which are highly concentrated bioactive components of colostrum, with the mechanisms related to FcRn endosome action. In addition to secretion, we highlight the recent findings of a role of the FcRn in phagocytosis and antigen presentation and relate its significant and abrupt change in cellular location after parturition to a role in the prevention and resistance to mastitis infections.</p>","PeriodicalId":16413,"journal":{"name":"Journal of Mammary Gland Biology and Neoplasia","volume":" ","pages":"419-453"},"PeriodicalIF":2.5,"publicationDate":"2021-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39963734","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":"Mammary Development and Breast Cancer: a Notch Perspective.","authors":"Weizhen Chen,&nbsp;Wei Wei,&nbsp;Liya Yu,&nbsp;Zi Ye,&nbsp;Fujing Huang,&nbsp;Liyan Zhang,&nbsp;Shiqi Hu,&nbsp;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}

{"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}