{"title":"Exploring the One Health Paradigm in Male Breast Cancer","authors":"Kirsty Luo-Yng Tay, George Cowan, Subarnarekha Chatterji, Giulia Conti, Valerie Speirs","doi":"10.1007/s10911-024-09560-6","DOIUrl":"https://doi.org/10.1007/s10911-024-09560-6","url":null,"abstract":"<p>How cancer patterns in humans compare to those of other species remains largely unknown and there is an even bigger knowledge gap for rare cancers like male breast cancer. One Health is a convergence of human and animal healthcare that encourages cross-pollination of medical research uniting human and veterinary medicine. Recognising that breast cancer occurs spontaneously in other male species (e.g. primates, canines, felines), and knowing that no laboratory models exist for male breast cancer, which limits our ability to perform functional studies, we explored the feasibility of applying One Health to breast cancer in men by conducting a narrative review of the topic. Spontaneous development of breast cancer was reported in captive male primates and in companion canines and felines. Some parallels in tumour biology of human male breast cancer with canines and primates were found. The age distribution, pattern of biomarker expression and metastasis were similar, with mammary tumours typically detected after two-thirds of average lifespan. However, instances of triple negative and inflammatory breast cancer, which are rarely observed in human male breast cancer, were found in canines and histological classification was inconsistent between species. These disparities need redressing to enable full exploration of the One Health paradigm in rare cancers.</p>","PeriodicalId":16413,"journal":{"name":"Journal of Mammary Gland Biology and Neoplasia","volume":"44 1","pages":""},"PeriodicalIF":2.5,"publicationDate":"2024-04-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140579564","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":"Using Organoids to Tap Mammary Gland Diversity for Novel Insight.","authors":"Gat Rauner","doi":"10.1007/s10911-024-09559-z","DOIUrl":"10.1007/s10911-024-09559-z","url":null,"abstract":"<p><p>This article offers a comprehensive perspective on the transformative role of organoid technology on mammary gland biology research across a diverse array of mammalian species.The mammary gland's unique development and regenerative capabilities render this organ an ideal model for studying developmental evolution, stem cell behavior, and regenerative processes. The discussion extends to the use of cross-species mammary organoids to address key biological inquiries in evolution, tissue regeneration, cancer research, and lactation, highlighting the limitations of traditional mouse models and the benefits of incorporating a more diverse range of animal models.Advances in organoid biology have been critical in overcoming ethical and practical constraints of in-vivo studies, especially in human research. The generation of human and mouse mammary organoids that faithfully recapitulate in-vivo tissues marks a significant stride in this field. Parallel capabilities are now emerging for other mammals, as well.Utilizing mammary organoids from various species has the potential to make invaluable contributions to our understanding of mammary gland biology, with implications for regenerative medicine, cancer research, and lactation studies, thereby contributing to advancements in human health, agriculture, and nutrition science.</p>","PeriodicalId":16413,"journal":{"name":"Journal of Mammary Gland Biology and Neoplasia","volume":"29 1","pages":"7"},"PeriodicalIF":2.5,"publicationDate":"2024-03-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10972946/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140305853","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 Lymphatic System in Mammary Gland Biology and Breast Cancer.","authors":"Traci R Lyons, Esta Sterneck","doi":"10.1007/s10911-024-09558-0","DOIUrl":"10.1007/s10911-024-09558-0","url":null,"abstract":"","PeriodicalId":16413,"journal":{"name":"Journal of Mammary Gland Biology and Neoplasia","volume":"29 1","pages":"6"},"PeriodicalIF":2.5,"publicationDate":"2024-03-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10944808/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140143700","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}
Leena M Koskinen, Lari Nieminen, Antti Arjonen, Camilo Guzmán, Markus Peurla, Emilia Peuhu
{"title":"Spatial Engineering of Mammary Epithelial Cell Cultures with 3D Bioprinting Reveals Growth Control by Branch Point Proximity.","authors":"Leena M Koskinen, Lari Nieminen, Antti Arjonen, Camilo Guzmán, Markus Peurla, Emilia Peuhu","doi":"10.1007/s10911-024-09557-1","DOIUrl":"10.1007/s10911-024-09557-1","url":null,"abstract":"<p><p>The three-dimensional (3D) structure of the ductal epithelium and the surrounding extracellular matrix (ECM) are integral aspects of the breast tissue, and they have important roles during mammary gland development, function and malignancy. However, the architecture of the branched mammary epithelial network is poorly recapitulated in the current in vitro models. 3D bioprinting is an emerging approach to improve tissue-mimicry in cell culture. Here, we developed and optimized a protocol for 3D bioprinting of normal and cancerous mammary epithelial cells into a branched Y-shape to study the role of cell positioning in the regulation of cell proliferation and invasion. Non-cancerous cells formed continuous 3D cell networks with several organotypic features, whereas the ductal carcinoma in situ (DCIS) -like cancer cells exhibited aberrant basal polarization and defective formation of the basement membrane (BM). Quantitative analysis over time demonstrated that both normal and cancerous cells proliferate more at the branch tips compared to the trunk region of the 3D-bioprinted cultures, and particularly at the tip further away from the branch point. The location-specific rate of proliferation was independent of TGFβ signaling but invasion of the DCIS-like breast cancer cells was reduced upon the inhibition of TGFβ. Thus, our data demonstrate that the 3D-bioprinted cells can sense their position in the branched network of cells and proliferate at the tips, thus recapitulating this feature of mammary epithelial branching morphogenesis. In all, our results demonstrate the capacity of the developed 3D bioprinting method for quantitative analysis of the relationships between tissue structure and cell behavior in breast morphogenesis and cancer.</p>","PeriodicalId":16413,"journal":{"name":"Journal of Mammary Gland Biology and Neoplasia","volume":"29 1","pages":"5"},"PeriodicalIF":3.0,"publicationDate":"2024-02-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10902034/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139983155","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":"Protocols for Co-Culture Phenotypic Assays with Breast Cancer Cells and THP-1-Derived Macrophages.","authors":"Alicja Mazan, Anna A Marusiak","doi":"10.1007/s10911-024-09556-2","DOIUrl":"10.1007/s10911-024-09556-2","url":null,"abstract":"<p><p>Tumor mass comprises not only cancer cells but also heterogeneous populations of immune and stromal cells, along with the components of the extracellular matrix, collectively called the tumor microenvironment (TME). This diverse population of cells can communicate with each other, which can positively or negatively affect tumor growth and progression to malignancy. The most common type of immune cells in the TME are macrophages. Macrophages continuously differentiate into a broad landscape of tumor-associated macrophages (TAMs) in response to numerous signals from the TME, which makes studies on TAMs quite challenging. Therefore, implementing reliable protocols is a milestone for drawing consistent conclusions about the interactions between cancer cells and TAMs. Here, we provide the details for the polarization of a human leukemia monocytic cell line, THP-1, into M0, M1 and M2 macrophages. We also present a step-by-step protocol for a transwell co-culture using a human breast cancer cell line, HCC1806, and THP-1-derived macrophages. Finally, we describe the colony formation and migration assays performed on the breast cancer cells after the co-culture with macrophages to measure the influence of macrophages on the oncogenic features of cancer cells. In summary, our co-culture-based protocols can be a valuable resource for investigating the interactions between macrophages and cancer cells.</p>","PeriodicalId":16413,"journal":{"name":"Journal of Mammary Gland Biology and Neoplasia","volume":"29 1","pages":"4"},"PeriodicalIF":2.5,"publicationDate":"2024-02-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10858929/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139716109","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":"Fast Ultrasound Scanning is a Rapid, Sensitive, Precise and Cost-Effective Method to Monitor Tumor Grafts in Mice.","authors":"Sébastien Molière, Arthur Martinet, Amélie Jaulin, Massimo Lodi, Thien-Nga Chamaraux-Tran, Fabien Alpy, Guillaume Bierry, Catherine Tomasetto","doi":"10.1007/s10911-024-09555-3","DOIUrl":"10.1007/s10911-024-09555-3","url":null,"abstract":"<p><p>In preclinical studies, accurate monitoring of tumor dynamics is crucial for understanding cancer biology and evaluating therapeutic interventions. Traditional methods like caliper measurements and bioluminescence imaging (BLI) have limitations, prompting the need for improved imaging techniques. This study introduces a fast-scan high-frequency ultrasound (HFUS) protocol for the longitudinal assessment of syngeneic breast tumor grafts in mice, comparing its performance with caliper, BLI measurements and with histological analysis. The E0771 mammary gland tumor cell line, engineered to express luciferase, was orthotopically grafted into immunocompetent C57BL/6 mice. Tumor growth was monitored longitudinally at multiple timepoints using caliper measurement, HFUS, and BLI, with the latter two modalities assessed against histopathological standards post-euthanasia. The HFUS protocol was designed for rapid, anesthesia-free scanning, focusing on volume estimation, echogenicity, and necrosis visualization. All mice developed tumors, only 20.6% were palpable at day 4. HFUS detected tumors as small as 2.2 mm in average diameter from day 4 post-implantation, with an average scanning duration of 47 s per mouse. It provided a more accurate volume assessment than caliper, with a lower average bias relative to reference tumor volume. HFUS also revealed tumor necrosis, correlating strongly with BLI in terms of tumor volume and cellularity. Notable discrepancies between HFUS and BLI growth rates were attributed to immune cell infiltration. The fast HFUS protocol enables precise and efficient tumor assessment in preclinical studies, offering significant advantages over traditional methods in terms of speed, accuracy, and animal welfare, aligning with the 3R principle in animal research.</p>","PeriodicalId":16413,"journal":{"name":"Journal of Mammary Gland Biology and Neoplasia","volume":"29 1","pages":"2"},"PeriodicalIF":3.0,"publicationDate":"2024-01-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10827948/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139576200","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}
Jenelys Ruiz Ortiz, Steven M Lewis, Michael Ciccone, Deeptiman Chatterjee, Samantha Henry, Adam Siepel, Camila O Dos Santos
{"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}
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
{"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}
Nikolina Giotopoulou, Wenyang Shi, Malgorzata Maria Parniewska, Wenwen Sun, Jonas Fuxe
{"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}