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Breast Cancer Stroma

Cecilia W Huo, Prue Hill, Grace Chew, Paul J Neeson, Heloise Halse, Elizabeth D Williams, Michael A Henderson, Erik W Thompson, Kara L Britt
BACKGROUND: Epidemiological studies have consistently shown that increased mammographic density (MD) is a strong risk factor for breast cancer. We previously observed an elevated number of vimentin+ /CD45+ leukocytes in high MD (HMD) epithelium. In the present study, we aimed to investigate the subtypes of immune cell infiltrates in HMD and low MD (LMD) breast tissue. METHODS: Fifty-four women undergoing prophylactic mastectomy at Peter MacCallum Cancer Centre or St...
August 9, 2018: Breast Cancer Research: BCR
Benjamin D Landry, Thomas Leete, Ryan Richards, Peter Cruz-Gordillo, Hannah R Schwartz, Megan E Honeywell, Gary Ren, Alyssa D Schwartz, Shelly R Peyton, Michael J Lee
Due to tumor heterogeneity, most believe that effective treatments should be tailored to the features of an individual tumor or tumor subclass. It is still unclear, however, what information should be considered for optimal disease stratification, and most prior work focuses on tumor genomics. Here, we focus on the tumor microenvironment. Using a large-scale coculture assay optimized to measure drug-induced cell death, we identify tumor-stroma interactions that modulate drug sensitivity. Our data show that the chemo-insensitivity typically associated with aggressive subtypes of breast cancer is not observed if these cells are grown in 2D or 3D monoculture, but is manifested when these cells are cocultured with stromal cells, such as fibroblasts...
August 6, 2018: Molecular Systems Biology
Whitney R Grither, Gregory D Longmore
The action of the collagen binding receptor tyrosine kinase (RTK) discoidin domain receptor 2 (DDR2) in both tumor and tumor stromal cells has been established as critical for breast cancer metastasis. Small molecule inhibitors that target the extracellular domain of RTKs are rare, as they have classically been regarded as too small to block binding with large polypeptide ligands. Here, we report the identification and characterization of a selective, extracellularly acting small molecule inhibitor (WRG-28) of DDR2 that uniquely inhibits receptor-ligand interactions via allosteric modulation of the receptor...
July 30, 2018: Proceedings of the National Academy of Sciences of the United States of America
Yue Du, Roy Zhang, Abolfazl Zargari, Theresa C Thai, Camille C Gunderson, Katherine M Moxley, Hong Liu, Bin Zheng, Yuchen Qiu
The tumor-stroma ratio (TSR) reflected on hematoxylin and eosin (H&E)-stained histological images is a potential prognostic factor for survival. Automatic image processing techniques that allow for high-throughput and precise discrimination of tumor epithelium and stroma are required to elevate the prognostic significance of the TSR. As a variant of deep learning techniques, transfer learning leverages nature-images features learned by deep convolutional neural networks (CNNs) to relieve the requirement of deep CNNs for immense sample size when handling biomedical classification problems...
July 26, 2018: Annals of Biomedical Engineering
Hendrika M Duivenvoorden, Alex Spurling, Sandra A O'Toole, Belinda S Parker
Mammographic screening has led to increased detection of breast cancer at a pre-invasive state, hence modelling the earliest stages of breast cancer invasion is important in defining candidate biomarkers to predict risk of relapse. Discrimination of pre-invasive from invasive lesions is critically important for such studies. Myoepithelial cells are the barrier between epithelial cells and the surrounding stroma in the breast ductal system. A number of myoepithelial immunohistochemistry markers have been identified and validated in human tissue for use by pathologists as diagnostic tools to distinguish in situ carcinoma from invasive breast cancer...
2018: PloS One
Philip A Doble, George L Gabor Miklos
Many cancers are variably resistant to radiation treatment: some patients die within months, while others with the same tumour type and equivalent radiation protocol, survive for years. To determine why some tumours are radiosensitive, while others return after radiotherapy, requires new non-traditional approaches to oncology. Herein we used laser ablation-inductively coupled plasma-mass spectrometry (LA-ICP-MS) to test the hypothesis that Mn functions as a metabolic radioprotector and is an apex predictor of tumour radioresponsiveness...
July 20, 2018: Metallomics: Integrated Biometal Science
Mu Yang, Zhenhua Li, Meijing Ren, Shuai Li, Lanjing Zhang, Xinmin Zhang, Fangfang Liu
Aims: Tumor associated macrophages (TAMs) play a critical role in the initiation and progression of breast cancer. However, their prognostic significance in the molecular subtype of basal-like breast cancer (BLBC) is poorly understood. The aim of this study was to investigate the extent and patterns of TAMs in BLBC and their associations with clinicopathological features and patient survival. Methods and Results: We evaluated TAMs in 200 cases of BLBC by immunohistochemistry using the M2 macrophage marker CD163 and the pan-macrophage marker CD68 in tumor nest and stroma, and assessed their prognostic significance...
2018: Journal of Cancer
Gina M Sizemore, Subhasree Balakrishnan, Katie A Thies, Anisha M Hammer, Steven T Sizemore, Anthony J Trimboli, Maria C Cuitiño, Sarah A Steck, Gary Tozbikian, Raleigh D Kladney, Neelam Shinde, Manjusri Das, Dongju Park, Sarmila Majumder, Shiva Krishnan, Lianbo Yu, Soledad A Fernandez, Arnab Chakravarti, Peter G Shields, Julia R White, Lisa D Yee, Thomas J Rosol, Thomas Ludwig, Morag Park, Gustavo Leone, Michael C Ostrowski
The importance of the tumor-associated stroma in cancer progression is clear. However, it remains uncertain whether early events in the stroma are capable of initiating breast tumorigenesis. Here, we show that in the mammary glands of non-tumor bearing mice, stromal-specific phosphatase and tensin homolog (Pten) deletion invokes radiation-induced genomic instability in neighboring epithelium. In these animals, a single dose of whole-body radiation causes focal mammary lobuloalveolar hyperplasia through paracrine epidermal growth factor receptor (EGFR) activation, and EGFR inhibition abrogates these cellular changes...
July 17, 2018: Nature Communications
Tao Jiang, Jose Munguia-Lopez, Salvador Flores-Torres, Joel Grant, Sanahan Vijayakumar, Antonio De Leon-Rodriguez, Joseph M Kinsella
The cellular, biochemical, and biophysical heterogeneity of the native tumor microenvironment is not recapitulated by growing immortalized cancer cell lines using conventional two-dimensional (2D) cell culture. These challenges can be overcome by using bioprinting techniques to build heterogeneous three-dimensional (3D) tumor models whereby different types of cells are embedded. Alginate and gelatin are two of the most common biomaterials employed in bioprinting due to their biocompatibility, biomimicry, and mechanical properties...
July 2, 2018: Journal of Visualized Experiments: JoVE
Ernestina M De Francesco, Marcello Maggiolini, Anna Maria Musti
The Notch signaling pathway acts in both physiological and pathological conditions, including embryonic development and tumorigenesis. In cancer progression, diverse mechanisms are involved in Notch-mediated biological responses, including angiogenesis and epithelial-mesenchymal-transition (EMT). During EMT, the activation of cellular programs facilitated by transcriptional repressors results in epithelial cells losing their differentiated features, like cell⁻cell adhesion and apical⁻basal polarity, whereas they gain motility...
July 10, 2018: International Journal of Molecular Sciences
Janine Hensel, Antoinette Wetterwald, Ramzi Temanni, Irene Keller, Carsten Riether, Gabri van der Pluijm, Marco G Cecchini, George N Thalmann
Prostate and breast cancers frequently metastasize to bone. The physiological bone homeostasis is perturbed once cancer cells proliferate at the bone metastatic site. Tumors are complex structures consisting of cancer cells and numerous stroma cells. In this study, we show that osteolytic cancer cells (PC-3 and MDA-MB231) induce transcriptome changes in the bone/bone marrow microenvironment (stroma). This stroma transcriptome differs from the previously reported stroma transcriptome of osteoinductive cancer cells (VCaP)...
June 22, 2018: Oncotarget
Philipp Mertins, Lauren C Tang, Karsten Krug, David J Clark, Marina A Gritsenko, Lijun Chen, Karl R Clauser, Therese R Clauss, Punit Shah, Michael A Gillette, Vladislav A Petyuk, Stefani N Thomas, D R Mani, Filip Mundt, Ronald J Moore, Yingwei Hu, Rui Zhao, Michael Schnaubelt, Hasmik Keshishian, Matthew E Monroe, Zhen Zhang, Namrata D Udeshi, Deepak Mani, Sherri R Davies, R Reid Townsend, Daniel W Chan, Richard D Smith, Hui Zhang, Tao Liu, Steven A Carr
Here we present an optimized workflow for global proteome and phosphoproteome analysis of tissues or cell lines that uses isobaric tags (TMT (tandem mass tags)-10) for multiplexed analysis and relative quantification, and provides 3× higher throughput than iTRAQ (isobaric tags for absolute and relative quantification)-4-based methods with high intra- and inter-laboratory reproducibility. The workflow was systematically characterized and benchmarked across three independent laboratories using two distinct breast cancer subtypes from patient-derived xenograft models to enable assessment of proteome and phosphoproteome depth and quantitative reproducibility...
July 9, 2018: Nature Protocols
K M H Vangangelt, L S A Tollenaar, G W van Pelt, E M de Kruijf, T J A Dekker, P J K Kuppen, R A E M Tollenaar, W E Mesker
The tumor-stroma ratio (TSR) has previously been found to be a strong prognostic parameter in primary breast cancer tumors. Since the presence of tumor cells in lymph nodes is important for clinical decision making, the influence of TSR in the primary breast tumor combined with the TSR in tumor-positive lymph nodes on prognosis was evaluated. Women with invasive breast cancer without distant metastasis who underwent an axillary lymph node dissection between 1985 and 1994 at the Leiden University Medical Center were retrospectively analyzed...
July 6, 2018: International Journal of Cancer. Journal International du Cancer
Diana Martins, Fernando Schmitt
It is now widely accepted that the tumor microenvironment is a pathologically active niche that shapes tumor nature, evolution and response to treatment. Close interactions between cancer cells and stroma are known to regulate several cancer pathways and thus the determination of different tumor-stromal interactions could be an important step in invasiveness. The breast cancer microenvironment is a complex combination of several different cell types and molecules and a key contributor to tumor development and progression...
July 6, 2018: Histology and Histopathology
Alexandra R Harris, Matthew J Perez, Jennifer M Munson
BACKGROUND: Infiltration into lymphatic vessels is a critical step in breast cancer metastasis. Lymphatics undergo changes that facilitate metastasis as a result of activation of the cells lining lymphatic vessels, lymphatic endothelial cells (LECs). Inhibition of activation by targeting VEGFR3 can reduce invasion toward lymphatics. To best benefit patients, this approach should be coupled with standard of care that slows tumor growth, such as chemotherapy. Little is known about how chemotherapies, like docetaxel, may influence lymphatics and conversely, how lymphatics can alter responses to therapy...
July 6, 2018: BMC Cancer
Timothy Kwang Yong Tay, Peiyong Guan, Benjamin Nathanael Loke, Nur Diyana Md Nasir, Vikneswari Rajasegaran, Aye Aye Thike, Derrick Lian, Kenneth Tou En Chang, Bin Tean Teh, Cedric Chuan Young Ng, Puay Hoon Tan
AIM: This study aims to examine the molecular genetics of paediatric breast fibroepithelial tumours through targeted sequencing of 50 genes. MATERIALS AND METHODS: Formalin fixed paraffin embedded tissue of fibroepithelial tumours diagnosed in a cohort of patients aged 18 years and below were subjected to next generation sequencing using the Haloplex Target Enrichment System (Agilent). RESULTS: Twenty-five conventional and seventeen juvenile fibroadenomas were studied, with MED12 mutations found in 53...
July 3, 2018: Histopathology
C Coulson-Gilmer, M P Humphries, S Sundara Rajan, A Droop, S Jackson, A Condon, G Cserni, L B Jordan, J L Jones, R Kanthan, A Di Benedetto, M Mottolese, E Provenzano, J Kulka, A M Shaaban, A M Hanby, V Speirs
Breast cancer can arise in either gender; however, it is rare in men, accounting for <1% of diagnosed cases. In a previous transcriptomic screen of male and female breast cancer we observed that Stanniocalcin 2 (STC2) was overexpressed in the former. The aim of this study was to confirm the expression of STC2 in male breast cancer, and to investigate whether this had an impact on patient prognosis. Following an earlier transcriptomic screen, STC2 gene expression was confirmed by RT-qPCR in matched male and female BC samples as well as in tumour-associated fibroblasts derived from each gender...
June 28, 2018: Journal of Pathology. Clinical Research
Xinyan Wu, Muhammad Saddiq Zahari, Santosh Renuse, Nandini A Sahasrabuddhe, Raghothama Chaerkady, Min-Sik Kim, Mary Jo Fackler, Martha Stampfer, Edward Gabrielson, Saraswati Sukumar, Akhilesh Pandey
Background: Cancer-associated fibroblasts (CAFs) are one of the most important components of tumor stroma and play a key role in modulating tumor growth. However, a mechanistic understanding of how CAFs communicate with tumor cells to promote their proliferation and invasion is far from complete. A major reason for this is that most current techniques and model systems do not capture the complexity of signal transduction that occurs between CAFs and tumor cells. Methods: In this study, we employed a stable isotope labeling with amino acids in cell culture (SILAC) strategy to label invasive breast cancer cells, MDA-MB-231, and breast cancer patient-derived CAF this has already been defined above cells...
2018: Clinical Proteomics
Nancy Adriana Espinoza-Sánchez, Jennifer Enciso, Rosana Pelayo, Ezequiel M Fuentes-Pananá
Breast cancer is a complex disease exhibiting extensive inter- and intra-tumor heterogeneity. Inflammation is a well-known driver of cancer progression, often attributed to immune cells infiltrating the tumor stroma. However, tumor cells themselves are capable to secrete a variety of inflammatory molecules, of which we understand very little about their role in intra-clonal communication. We recently reported the capacity of triple negative cell lines to induce a cancer stem cell (CSC)-like phenotype and invasion properties into luminal cells, a mechanism mediated by pro-inflammatory cytokines that up-regulated the CXCL12/CXCR4/CXCR7 chemokine signaling axis...
June 1, 2018: Oncotarget
Babak Ehteshami Bejnordi, Maeve Mullooly, Ruth M Pfeiffer, Shaoqi Fan, Pamela M Vacek, Donald L Weaver, Sally Herschorn, Louise A Brinton, Bram van Ginneken, Nico Karssemeijer, Andrew H Beck, Gretchen L Gierach, Jeroen A W M van der Laak, Mark E Sherman
The breast stromal microenvironment is a pivotal factor in breast cancer development, growth and metastases. Although pathologists often detect morphologic changes in stroma by light microscopy, visual classification of such changes is subjective and non-quantitative, limiting its diagnostic utility. To gain insights into stromal changes associated with breast cancer, we applied automated machine learning techniques to digital images of 2387 hematoxylin and eosin stained tissue sections of benign and malignant image-guided breast biopsies performed to investigate mammographic abnormalities among 882 patients, ages 40-65 years, that were enrolled in the Breast Radiology Evaluation and Study of Tissues (BREAST) Stamp Project...
June 13, 2018: Modern Pathology: An Official Journal of the United States and Canadian Academy of Pathology, Inc
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