Journal of Mammary Gland Biology and Neoplasia最新文献

{"title":"High-fat diet, but not duration of lactation, increases mammary gland lymphatic vessel function and subsequent growth of inflammatory breast cancer cells.","authors":"Wintana Balema, Janelle Morton, Richard A Larson, Li Li, Fred Christian Velasquez, Natalie W Fowlkes, Savitri Krishnamurthy, Bisrat G Debeb, Eva Sevick-Muraca, Wendy A Woodward","doi":"10.1007/s10911-023-09548-8","DOIUrl":"10.1007/s10911-023-09548-8","url":null,"abstract":"<p><p>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 IBC tumor growth; and on aspects of the mammary gland microenvironment before and after IBC (SUM149) xenograft inoculation. We hypothesized that weaning status and diet would have synergistic effects on lymphatic function and the breast microenvironment to enhance IBC tumor growth. Changes in lymphatic structure and function were characterized with in vivo near-infrared fluorescence (NIRF) imaging. Mice were fed either a high-fat diet (HFD; 60 kcal%) or a normal/low-fat diet (LFD; 10 kcal%), bred twice, and subjected to either normal-duration nursing (NW) or forced weaning (FW). SUM149 IBC tumors were implanted at 14 months; images were obtained before and after implantation. Multiparous mice fed HFD showed increased pre-tumor lymphatic pulsing in both the FW and NW groups relative to mice fed LFD. HFD promoted tumor growth independent of weaning time (P = 0.04). Pre-tumor lymphatic pulsing was associated with tumor volume at 8 weeks (P = 0.02) and was significantly correlated with expression of the lymphatic tracking ligand CCL21 (P = 0.05, Table 1). HFD significantly increased the numbers of monocyte-derived IBA1⁺, CD163⁺, and CD11c⁺ cells (P < 0.0001, P < 0.0001, P = 0.0005) in the contralateral, non-tumor-bearing mammary gland. Numbers of lymphangiogenic podoplanin⁺/IBA1⁺ macrophages were increased in the ducts of HFD and FW mice (all P < 0.003). HFD in nulliparous mice had a similar increase in lymphatic pulsing at 14 weeks (P = 0.006), indicating that this functional change was independent of parity. We conclude that HFD induced increases in mammary gland lymphatic function, assessed as pulsing rate before tumor initiation, and correlated with inflammation in the mammary gland and increased SUM149 tumor growth. The relationship between diet, lymphatic pulsing, and tumor growth warrants further investigation.</p>","PeriodicalId":16413,"journal":{"name":"Journal of Mammary Gland Biology and Neoplasia","volume":null,"pages":null},"PeriodicalIF":2.5,"publicationDate":"2023-10-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10558390/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41157026","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":"RETRACTED ARTICLE: Pure Primary Squamous Cell Carcinoma of the Breast Arising from the Epithelium of a Complex Mammary Cyst: A Case Report.","authors":"Deniz Tihan, Gülcin Hepgul, Meltem Kucukyilmaz, Mehmet Sar, Hakan Guven","doi":"10.1007/s10911-011-9208-2","DOIUrl":"10.1007/s10911-011-9208-2","url":null,"abstract":"","PeriodicalId":16413,"journal":{"name":"Journal of Mammary Gland Biology and Neoplasia","volume":null,"pages":null},"PeriodicalIF":3.0,"publicationDate":"2023-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10384523","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":"Non-Linear Lymphatic Anatomy in Breast Cancer Patients Prior to Axillary Lymph Node Dissection: A Risk Factor For Lymphedema Development.","authors":"JacqueLyn R Kinney,&nbsp;Rosie Friedman,&nbsp;Erin Kim,&nbsp;Elizabeth Tillotson,&nbsp;Kathy Shillue,&nbsp;Bernard T Lee,&nbsp;Dhruv Singhal","doi":"10.1007/s10911-023-09545-x","DOIUrl":"https://doi.org/10.1007/s10911-023-09545-x","url":null,"abstract":"<p><p>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 lymphatic channels visualized on ICG, representing a non-diseased state, some patients demonstrate non-linear patterns. This study aims to determine potential inciting factors that help explain why some patients have non-linear patterns, and what these patterns represent regarding the relative risk of developing postoperative breast cancer related lymphedema in this population. A retrospective review was conducted to identify breast cancer patients who underwent successful ILR with preoperative ICG at our institution from November 2017-June 2022. Among the 248 patients who were identified, 13 (5%) had preoperative non-linear lymphatic anatomy. A history of trauma or surgery of the affected limb and an increasing number of sentinel lymph nodes removed prior to ALND appeared to be risk factors for non-linear lymphatic anatomy. Furthermore, non-linear anatomy in the limb of interest was associated with an increased risk of postoperative lymphedema development. Overall, non-linear lymphatic anatomy on pre-operative ICG lymphography appears to be a risk factor for developing ipsilateral breast cancer-related lymphedema. Guided by the study's findings, when breast cancer patients present with baseline non-linear lymphatic anatomy, our institution has implemented a protocol of prophylactically prescribing compression sleeves immediately following ALND.</p>","PeriodicalId":16413,"journal":{"name":"Journal of Mammary Gland Biology and Neoplasia","volume":null,"pages":null},"PeriodicalIF":2.5,"publicationDate":"2023-07-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10363047/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10220810","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":"Distinct Requirements for Adaptor Proteins NCK1 and NCK2 in Mammary Gland Development.","authors":"Adam P Golding,&nbsp;Benjamin Ferrier,&nbsp;Laura A New,&nbsp;Peihua Lu,&nbsp;Claire E Martin,&nbsp;Erka Shata,&nbsp;Robert A Jones,&nbsp;Roger A Moorehead,&nbsp;Nina Jones","doi":"10.1007/s10911-023-09541-1","DOIUrl":"https://doi.org/10.1007/s10911-023-09541-1","url":null,"abstract":"<p><p>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 expression profiles between the two paralogs. Nck1 showed widespread expression in luminal, basal, stromal and endothelial cells, while Nck2 was restricted to luminal and basal cells, with prominent enrichment in hormone-sensing luminal subtypes. Next, using mice with global knockout of Nck1 or Nck2, we assessed mammary gland development during and after puberty (5, 8 and 12 weeks of age). Mice lacking Nck1 or Nck2 displayed significant defects in ductal outgrowth and branching at 5 weeks compared to controls, and the defects persisted in Nck2 knockout mice at 8 weeks before normalizing at 12 weeks. These defects were accompanied by an increase in epithelial cell proliferation at 5 weeks and a decrease at 8 weeks in both Nck1 and Nck2 knockout mice. We also profiled expression of several key genes associated with mammary gland development at these timepoints and detected temporal changes in transcript levels of hormone receptors as well as effectors of cell proliferation and migration in Nck1 and Nck2 knockout mice, in line with the distinct phenotypes observed at 5 and 8 weeks. Together these studies reveal a requirement for NCK proteins in mammary gland morphogenesis, and suggest that deregulation of Nck expression could drive breast cancer progression and metastasis.</p>","PeriodicalId":16413,"journal":{"name":"Journal of Mammary Gland Biology and Neoplasia","volume":null,"pages":null},"PeriodicalIF":2.5,"publicationDate":"2023-07-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10361900/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9854036","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":"Imagine beyond: recent breakthroughs and next challenges in mammary gland biology and breast cancer research.","authors":"Renée van Amerongen, Mohamed Bentires-Alj, Antonius L van Boxtel, Robert B Clarke, Silvia Fre, Eva Gonzalez Suarez, Richard Iggo, Martin Jechlinger, Jos Jonkers, Marja L Mikkola, Zuzana Sumbalova Koledova, Therese Sørlie, Maria dM Vivanco","doi":"10.1007/s10911-023-09544-y","DOIUrl":"10.1007/s10911-023-09544-y","url":null,"abstract":"<p><p>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 to come. The outcomes of these discussions are presented in this position paper, in the hope that it will serve as a summary of the current state of affairs in mammary gland biology and breast cancer research for early career researchers and other newcomers in the field, and as inspiration for scientists and clinicians to move the field forward.</p>","PeriodicalId":16413,"journal":{"name":"Journal of Mammary Gland Biology and Neoplasia","volume":null,"pages":null},"PeriodicalIF":2.5,"publicationDate":"2023-07-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10349020/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9824299","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":"Studying Mammary Physiology and Pathology in Domestic Species Benefits Both Humans and Animals.","authors":"Katherine Hughes","doi":"10.1007/s10911-023-09547-9","DOIUrl":"10.1007/s10911-023-09547-9","url":null,"abstract":"","PeriodicalId":16413,"journal":{"name":"Journal of Mammary Gland Biology and Neoplasia","volume":null,"pages":null},"PeriodicalIF":2.5,"publicationDate":"2023-07-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10348960/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10199574","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":"Gestational Breast Cancer - a Review of Outcomes, Pathophysiology, and Model Systems.","authors":"Mackenzie K Callaway, Camila O Dos Santos","doi":"10.1007/s10911-023-09546-w","DOIUrl":"10.1007/s10911-023-09546-w","url":null,"abstract":"<p><p>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, prognosis remains dismal for patients with gestational breast cancer (GBC) and post-partum breast cancer (PPBC), as pregnancy and lactation pose additional complications and barriers to several gold standard clinical approaches. Moreover, delayed diagnosis and treatment, coupled with the aggressive time-scale in which GBC metastasizes, inevitably contributes to the higher incidence of disease recurrence and patient mortality. Therefore, there is an urgent and evident need to better understand the factors contributing to the establishment and spreading of BC during pregnancy. In this review, we provide a literature-based overview of the diagnostics and treatments available to patients with BC more broadly, and highlight the treatment deficit patients face due to gestational status. Further, we review the current understanding of the molecular and cellular mechanisms driving GBC, and discuss recent advances in model systems that may support the identification of targetable approaches to block BC development and dissemination during pregnancy. Our goal is to provide an updated perspective on GBC, and to inform critical areas needing further exploration to improve disease outcome.</p>","PeriodicalId":16413,"journal":{"name":"Journal of Mammary Gland Biology and Neoplasia","volume":null,"pages":null},"PeriodicalIF":2.5,"publicationDate":"2023-07-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10348943/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9823516","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":"SFRP1 Expression is Inversely Associated With Metastasis Formation in Canine Mammary Tumours.","authors":"Judith Seitz,&nbsp;Alan Bilsland,&nbsp;Chloé Puget,&nbsp;Ian Baasner,&nbsp;Robert Klopfleisch,&nbsp;Torsten Stein","doi":"10.1007/s10911-023-09543-z","DOIUrl":"https://doi.org/10.1007/s10911-023-09543-z","url":null,"abstract":"<p><strong>Background: </strong>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 with significantly different risk of distant metastasis formation. Here, we assessed whether expression patterns of these RNAs were also associated with canine tumour progression.</p><p><strong>Method: </strong>A sequential forward feature selection process was performed on a previously published microarray dataset of 27 CMTs with and without lymph node (LN) metastases to identify RNAs with significantly differential expression to identify prognostic genes within the 18-gene signature. Using an independent set of 33 newly identified archival CMTs, we compared expression of the identified prognostic subset on RNA and protein basis using RT-qPCR and immunohistochemistry on FFPE-tissue sections.</p><p><strong>Results: </strong>While the 18-gene signature as a whole did not have any prognostic power, a subset of three RNAs: Col13a1, Spock2, and Sfrp1, together completely separated CMTs with and without LN metastasis in the microarray set. However, in the new independent set assessed by RT-qPCR, only the Wnt-antagonist Sfrp1 showed significantly increased mRNA abundance in CMTs without LN metastases on its own (p = 0.013) in logistic regression analysis. This correlated with stronger SFRP1 protein staining intensity of the myoepithelium and/or stroma (p < 0.001). SFRP1 staining, as well as β-catenin membrane staining, was significantly associated with negative LN status (p = 0.010 and 0.014 respectively). However, SFRP1 did not correlate with β-catenin membrane staining (p = 0.14).</p><p><strong>Conclusion: </strong>The study identified SFRP1 as a potential biomarker for metastasis formation in CMTs, but lack of SFRP1 was not associated with reduced membrane-localisation of β-catenin in CMTs.</p>","PeriodicalId":16413,"journal":{"name":"Journal of Mammary Gland Biology and Neoplasia","volume":null,"pages":null},"PeriodicalIF":2.5,"publicationDate":"2023-07-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10319705/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9857251","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":"Deciphering Stromal Changes between Metastatic and Non-metastatic Canine Mammary Carcinomas.","authors":"Julia Ettlin, Alina Bauer, Lennart Opitz, Alexandra Malbon, Enni Markkanen","doi":"10.1007/s10911-023-09542-0","DOIUrl":"10.1007/s10911-023-09542-0","url":null,"abstract":"<p><p>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 compared to non-metastatic ones. To characterize stromal changes between metastatic and non-metastatic CMTs and identify potential drivers of tumour progression, we analysed CAS and matched normal stroma from 16 non-metastatic and 15 metastatic CMTs by RNA-sequencing of microdissected FFPE tissue. We identified 1438 differentially regulated genes between CAS and normal stroma, supporting previous results demonstrating stromal reprogramming in CMTs to be comparable with CAS in human breast cancer and validating deregulation of pathways and genes associated with CAS. Using primary human fibroblasts activated by treatment with TGFβ, we demonstrate some of the strongest expression changes to be conserved in fibroblasts across species. Furthermore, we identify 132 differentially expressed genes between CAS from metastatic and non-metastatic tumours, with strong changes in pathways including chemotaxis, regulation of apoptosis, immune response and TGFβ signalling and validate deregulation of several targets using RT-qPCR. Finally, we identify specific upregulation of COL6A5, F5, GALNT3, CIT and MMP11 in metastatic CAS, suggesting high stromal expression of these targets to be linked to malignancy and metastasis of CMTs. In summary, our data present a resource supporting further research into stromal changes of the mammary gland in relation to metastasis with implications for both canine and human mammary cancer.</p>","PeriodicalId":16413,"journal":{"name":"Journal of Mammary Gland Biology and Neoplasia","volume":null,"pages":null},"PeriodicalIF":2.5,"publicationDate":"2023-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10313573/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9799811","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":"PI3K inhibition circumvents resistance to SHP2 blockade in metastatic triple-negative breast cancer.","authors":"Romain J Amante, Charly Jehanno, Duvini De Silva, Marie-May Coissieux, Markus Ackerknecht, Vincent Romanet, Atul Sethi, Baptiste Hamelin, Bogdan-Tiberius Preca, Salvatore Piscuoglio, Charlotte K Y Ng, Morvarid Mohseni, Mohamed Bentires-Alj","doi":"10.1007/s10911-023-09539-9","DOIUrl":"10.1007/s10911-023-09539-9","url":null,"abstract":"<p><p>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 mechanisms of the resistance to these agents, nor the means to circumvent such resistance have been clearly defined. The PI3K signaling pathway is also hyperactivated in breast cancer and contributes to resistance to anticancer therapies. When PI3K is inhibited, resistance also develops for example via activation of RTKs. We therefore assessed the effect of targeting PI3K and SHP2 alone or in combination in preclinical models of metastatic TNBC. In addition to the beneficial inhibitory effects of SHP2 alone, dual PI3K/SHP2 treatment decreased primary tumor growth synergistically, blocked the formation of lung metastases, and increased survival in preclinical models. Mechanistically, transcriptome and phospho-proteome analyses revealed that resistance to SHP2 inhibition is mediated by PDGFRβ-evoked activation of PI3K signaling. Altogether, our data provide a rationale for co-targeting of SHP2 and PI3K in metastatic TNBC.</p>","PeriodicalId":16413,"journal":{"name":"Journal of Mammary Gland Biology and Neoplasia","volume":null,"pages":null},"PeriodicalIF":2.5,"publicationDate":"2023-06-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10256672/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9610401","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}