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...
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...
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...
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...
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...
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...
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...
On 8 December 2022 the organizing committee of the European Network for Breast Development and Cancer labs (ENBDC) held its fifth annual Think Tank meeting in Amsterdam, the Netherlands. Here, we embraced the opportunity to look back to identify the most prominent breakthroughs of the past ten years and to reflect on the main challenges that lie ahead for our field in the years...
The onset of pregnancy marks the start of offspring development, and represents the key physiological event that induces re-organization and specialization of breast tissue. Such drastic tissue remodeling has also been linked to epithelial cell transformation and the establishment of breast cancer (BC). While patient outcomes for BC overall continue to improve across subtypes...
Canine mammary tumours (CMTs) are the most frequent tumours in intact female dogs and show strong similarities with human breast cancer. In contrast to the human disease there are no standardised diagnostic or prognostic biomarkers available to guide treatment. We recently identified a prognostic 18-gene RNA signature that could stratify human breast cancer patients into groups...
Cancer-associated stroma (CAS) is widely recognized to influence development and progression of epithelial tumours including breast cancer. Canine mammary tumours (CMTs) such as simple canine mammary carcinomas represent valuable models for human breast cancer also with respect to stromal reprogramming. However, it remains unclear whether and how CAS changes in metastatic tumours...
The protein tyrosine phosphatase SHP2 activates oncogenic pathways downstream of most receptor tyrosine kinases (RTK) and has been implicated in various cancer types, including the highly aggressive subtype of triple-negative breast cancer (TNBC). Although allosteric inhibitors of SHP2 have been developed and are currently being evaluated in clinical trials, neither the...
Breast cancer is well-known to be a highly heterogenous disease. This facet of cancer makes finding a research model that mirrors the disparate intrinsic features challenging. With advances in multi-omics technologies, establishing parallels between the various models and human tumors is increasingly intricate. Here we review the various model systems and their relation to...
Many studies on bovine mammary glands focus on one stage of development. Often missing in those studies are repeated measures of development from the same animals. As milk production is directly affected by amount of parenchymal tissue within the udder, understanding mammary gland growth along with visualization of its structures during development is essential. Therefore...
The ERBB tyrosine kinase receptors and their ligands belong to a complex family that has diverse biological effects and expression profiles in the developing mammary glands, where its members play an essential role in translating hormone signals into local effects. While our understanding of these processes stems mostly from mouse models, there is the potential for differences in...
The role of fibroblast growth factor receptor 2 (FGFR2), an important mediator of stromal paracrine and autocrine signals, in mammary gland morphogenesis and breast cancer has been extensively studied over the last years. However, the function of FGFR2 signalling in the initiation of mammary epithelial oncogenic transformation remains elusive. Here, FGFR2-dependent behaviour of...
Mammary epithelial cells (MECs) are the only cell type that produces milk during lactation. MECs also form less-permeable tight junctions (TJs) to prevent the leakage of milk and blood components through the paracellular pathway (blood-milk barrier). Multiple factors that include hormones, cytokines, nutrition, and temperature regulate milk production and TJ formation in MECs...
Lactation is a physiological adaptation of the class Mammalia and is a product of over 200 million years of evolution. During lactation, the mammary gland orchestrates bone metabolism via serotonin signaling in order to provide sufficient calcium for the offspring in milk. The role of serotonin in bone remodeling was first discovered over two decades ago, and the interplay...
Mammary cancer is one of the most common neoplasms of dogs, primarily bitches. While studies have been carried out identifying differing risk of mammary neoplasia in different dog breeds, few studies have reported associations between dog breeds and clinical features such as number of neoplastic lesions found in an individual case or the likelihood of lesions being benign or...
The production of antimicrobial components and the formation of less-permeable tight junctions (TJs) are important in the defense system of lactating mammary glands and for safe dairy production. Valine is a branched-chain amino acid that is actively consumed in the mammary glands and promotes the production of major milk components like β-casein; additionally, branched-chain...
Determination of the mammary epithelial cell that serves as the cell of origin for breast cancer is key to understand tumor heterogeneity and clinical management. In this study, we aimed to decipher whether Rank expression in the presence of PyMT and Neu oncogenes might affect the cell of origin of mammary gland tumors. We observed that Rank expression in PyMT+/− and Neu...
The extracellular matrix (ECM) is biochemically and biomechanically important for the structure and function of the mammary gland, which undergoes vast structural changes throughout pubertal and reproductive development. Although hyaluronan (HA) is a ubiquitous glycosaminoglycan (GAG) of the mammary gland ECM, extensive characterization of HA deposition in the mammary gland is...