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Breast Cancer Stroma

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https://www.readbyqxmd.com/read/30325954/a-genomic-ruler-to-assess-oncogenic-transition-between-breast-tumor-and-stroma
#1
Shubhada Dhage, Amanda Ernlund, Kelly Ruggles, Deborah Axelrod, Russell Berman, Daniel Roses, Robert J Schneider
BACKGROUND: Cancers induce gene expression alterations in stroma surrounding tumors that supports cancer progression. However, it is actually not at all known the extent of altered stromal gene expression enacted by tumors nor the extent to which altered stromal gene expression penetrates the stromal tissue. Presently, post-surgical "tumor-free" stromal tissue is determined to be cancer-free based on solely on morphological normality-a criteria that has not changed in more than 100 years despite the existence of sophisticated gene expression data to the contrary...
2018: PloS One
https://www.readbyqxmd.com/read/30323895/ssecks-akap12-suppresses-metastatic-melanoma-lung-colonization-by-attenuating-src-mediated-pre-metastatic-niche-crosstalk
#2
Masashi Muramatsu, Shin Akakura, Lingqiu Gao, Jennifer Peresie, Benjamin Balderman, Irwin H Gelman
SSeCKS/Gravin/AKAP12 (SSeCKS) controls metastasis-associated PKC and Src signaling through direct scaffolding activity. SSeCKS is downregulated in the metastases of many human cancer types, and its forced re-expression suppresses the metastatic behavior of prostate cancer cells. SSeCKS is also downregulated in breast and prostate cancer stroma, and SSeCKS-null mice (KO) are metastasis-prone, suggesting a role in suppressing formation of the pre-metastatic niche. Here, we show that lung colonization and metastasis formation by B16F10 and SM1WT1[ Braf V600E ] mouse melanoma cells is 9-fold higher in syngeneic KO compared to WT hosts, although there is no difference in orthotopic tumor volumes...
September 11, 2018: Oncotarget
https://www.readbyqxmd.com/read/30317726/-clinicopathologic-features-of-breast-lymphoma-in-core-needle-biopsy
#3
J Rao, M Ruan, B H Yu, X Q Li, W T Yang, R H Shui
Objective: To investigate the clinicopathologic features and differential diagnosis of breast lymphoma in core needle biopsy. Methods: Seventy-two cases of breast lymphoma in core needle biopsy between 2011 and 2016 were extracted from the pathology database of Fudan University Shanghai Cancer Center. The clinicopathologic features were analyzed. The histological diagnosis of the tumors was based on the WHO classifications of tumors of hematopoietic and lymphoid tissues. Immunohistochemistry and molecular methods were performed to detect related antigens and genes...
October 8, 2018: Zhonghua Bing Li Xue za Zhi Chinese Journal of Pathology
https://www.readbyqxmd.com/read/30302588/the-prognostic-value-of-tumour-stroma-ratio-in-primary-breast-cancer-with-special-attention-to-triple-negative-tumours-a-review
#4
REVIEW
C J H Kramer, K M H Vangangelt, G W van Pelt, T J A Dekker, R A E M Tollenaar, W E Mesker
PURPOSE: There is a strong need to improve the prognostication of breast cancer patients in order to prevent over- and undertreatment, especially when considering adjuvant chemotherapy. Tumour stroma characteristics might be valuable in predicting disease progression. METHODS: Studies regarding the prognostic value of tumour-stroma ratio (TSR) in breast cancer are evaluated. RESULTS: A high stromal content is related to a relatively poor prognosis...
October 9, 2018: Breast Cancer Research and Treatment
https://www.readbyqxmd.com/read/30288360/il-6-augments-il-4-induced-polarization-of-primary-human-macrophages-through-synergy-of-stat3-stat6-and-batf-transcription-factors
#5
Sahil Gupta, Arpit Jain, Shahzad Nawaz Syed, Ryan G Snodgrass, Beatrice Pflüger-Müller, Matthias S Leisegang, Andreas Weigert, Ralf P Brandes, Ingo Ebersberger, Bernhard Brüne, Dmitry Namgaladze
Macrophages in the tumor microenvironment respond to complex cytokine signals. How these responses shape the phenotype of tumor-associated macrophages (TAMs) is incompletely understood. Here we explored how cytokines of the tumor milieu, interleukin (IL)-6 and IL-4, interact to influence target gene expression in primary human monocyte-derived macrophages (hMDMs). We show that dual stimulation with IL-4 and IL-6 synergistically modified gene expression. Among the synergistically induced genes are several targets with known pro-tumorigenic properties, such as CC-chemokine ligand 18 (CCL18), transforming growth factor alpha (TGFA) or CD274 (programmed cell death 1 ligand 1 (PD-L1))...
2018: Oncoimmunology
https://www.readbyqxmd.com/read/30269950/divergent-matrix-remodeling-strategies-distinguish-developmental-from-neoplastic-mammary-epithelial-cell-invasion-programs
#6
Tamar Y Feinberg, Huarui Zheng, Rui Liu, Max S Wicha, S Michael Yu, Stephen J Weiss
Metastasizing breast carcinoma cells have been hypothesized to mobilize tissue-invasive activity by co-opting the proteolytic systems employed by normal mammary epithelial cells undergoing branching morphogenesis. However, the critical effectors underlying morphogenesis remain unidentified, and their relationship to breast cancer invasion programs is yet to be established. Here, we identify the membrane-anchored matrix metalloproteinase, Mmp14/MT1-MMP, but not the closely related proteinase Mmp15/MT2-MMP, as the dominant proteolytic effector of both branching morphogenesis and carcinoma cell invasion in vivo...
September 24, 2018: Developmental Cell
https://www.readbyqxmd.com/read/30262850/somatic-trp53-mutations-differentially-drive-breast-cancer-and-evolution-of-metastases
#7
Yun Zhang, Shunbin Xiong, Bin Liu, Vinod Pant, Francis Celii, Gilda Chau, Ana C Elizondo-Fraire, Peirong Yang, Mingjian James You, Adel K El-Naggar, Nicholas E Navin, Guillermina Lozano
TP53 mutations are the most frequent genetic alterations in breast cancer and are associated with more aggressive disease and worse overall survival. We have created two conditional mutant Trp53 alleles in the mouse that allow expression of Trp53R172H or Trp53R245W missense mutations in single cells surrounded by a normal stroma and immune system. Mice with Trp53 mutations in a few breast epithelial cells develop breast cancers with high similarity to human breast cancer including triple negative. p53R245W tumors are the most aggressive and exhibit metastases to lung and liver...
September 27, 2018: Nature Communications
https://www.readbyqxmd.com/read/30237810/systematic-identification-of-the-key-candidate-genes-in-breast-cancer-stroma
#8
Yanxia Wang, Hui Xu, Baoan Zhu, Zhenling Qiu, Zaijun Lin
Background: Tumor microenvironment, in particular the stroma, plays an important role in breast cancer cell invasion and metastasis. Investigation of the molecular characteristics of breast cancer stroma may reveal targets for future study. Methods: The transcriptome profiles of breast cancer stroma and normal breast stroma were compared to identify differentially expressed genes (DEGs). The method was analysis of GSE26910 and GSE10797 datasets. Common DEGs were identified and then analyses of enriched pathways and hub genes were performed...
2018: Cellular & Molecular Biology Letters
https://www.readbyqxmd.com/read/30237579/fibulin-2-is-required-for-basement-membrane-integrity-of-mammary-epithelium
#9
Ayman M Ibrahim, Salwa Sabet, Akmal A El-Ghor, Nora Kamel, Shady E Anis, Joanna S Morris, Torsten Stein
Fibulin-2 (FBLN2) is a secreted extracellular matrix glycoprotein which has been associated with tissue development and remodelling. In the mouse mammary gland, FBLN2 can be detected during ductal morphogenesis in cap cells and myoepithelial cells at puberty and early pregnancy, respectively. In an attempt to assign its function, we knocked down Fbln2 in the mouse mammary epithelial cell line EpH4. FBLN2 reduction led to an increase in the size of spheroidal structures when compared to scrambled control shRNA-transduced cells plated on Matrigel matrix...
September 20, 2018: Scientific Reports
https://www.readbyqxmd.com/read/30196404/3d-bioprinting-and-stem-cells
#10
Caitlyn A Moore, Niloy N Shah, Caroline P Smith, Pranela Rameshwar
Three-dimensional (3D) in vitro modeling is increasingly relevant as two-dimensional (2D) cultures have been recognized with limits to recapitulate the complex endogenous conditions in the body. Additionally, fabrication technology is more accessible than ever. Bioprinting, in particular, is an additive manufacturing technique that expands the capabilities of in vitro studies by precisely depositing cells embedded within a 3D biomaterial scaffold that acts as temporary extracellular matrix (ECM). More importantly, bioprinting has vast potential for customization...
2018: Methods in Molecular Biology
https://www.readbyqxmd.com/read/30186741/elastin-molecular-aging-promotes-mda-mb-231-breast-cancer-cell-invasiveness
#11
Stéphanie Salesse, Ludivine Odoul, Lise Chazée, Christian Garbar, Laurent Duca, Laurent Martiny, Rachid Mahmoudi, Laurent Debelle
Elastin is a long-lived extracellular matrix protein responsible for the structural integrity and function of tissues. Breast cancer elastosis is a complex phenomenon resulting in both the deposition of elastotic masses and the local production of elastin fragments. In invasive human breast cancers, an increase in elastosis is correlated with severity of the disease and age of the patient. Elastin-derived peptides (EDPs) are a hallmark of aging and are matrikines - matrix fragments having the ability to regulate cell physiology...
September 2018: FEBS Open Bio
https://www.readbyqxmd.com/read/30185144/increased-insulin-like-growth-factor-1-production-by-polyploid-adipose-stem-cells-promotes-growth-of-breast-cancer-cells
#12
Roberta Fajka-Boja, Annamária Marton, Anna Tóth, Péter Blazsó, Vilmos Tubak, Balázs Bálint, István Nagy, Zoltán Hegedűs, Csaba Vizler, Robert L Katona
BACKGROUND: Adipose-tissue stem cells (ASCs) are subject of intensive research since their successful use in regenerative therapy. The drawback of ASCs is that they may serve as stroma for cancer cells and assist tumor progression. It is disquieting that ASCs frequently undergo genetic and epigenetic changes during their in vitro propagation. In this study, we describe the polyploidization of murine ASCs and the accompanying phenotypical, gene expressional and functional changes under long term culturing...
September 5, 2018: BMC Cancer
https://www.readbyqxmd.com/read/30177835/adipose-derived-stem-cells-enhance-human-breast-cancer-growth-and-cancer-stem-cell-like-properties-through-adipsin
#13
Hideaki Goto, Yohei Shimono, Yohei Funakoshi, Yoshinori Imamura, Masanori Toyoda, Naomi Kiyota, Seishi Kono, Shintaro Takao, Toru Mukohara, Hironobu Minami
Tumor microenvironment plays a key role for tumor development and progression. Although adipose tissue is a predominant component of stroma in mammary tissues and secretes various cytokines, chemokines and growth factors, roles of adipocytes in breast cancers remain to be elucidated. In this study, we found that adipsin, an adipokine secreted from mammary adipose tissues, enhanced proliferation and cancer stem cell (CSC)-like properties of human breast cancer patient-derived xenograft (PDX) cells. Adipsin was predominantly expressed in both adipose tissues of the surgical specimens of breast cancer patients and adipose-derived stem cells (ADSCs) isolated from them, and its expression level was significantly higher in obese patients...
September 3, 2018: Oncogene
https://www.readbyqxmd.com/read/30176263/activation-of-farnesoid-x-receptor-impairs-the-tumor-promoting-function-of-breast-cancer-associated-fibroblasts
#14
Ines Barone, Valentina Vircillo, Cinzia Giordano, Luca Gelsomino, Balázs Győrffy, Roberta Tarallo, Antonio Rinaldi, Giuseppina Bruno, Antonella Caruso, Francesco Romeo, Daniela Bonofiglio, Sebastiano Andò, Stefania Catalano
Cancer-associated Fibroblasts (CAFs), the principal components of tumor microenvironment, play multiple role in breast cancer progression. We have previously shown an oncosuppressive role of the nuclear Farnesoid X Receptor (FXR) in mammary epithelial cancer cells, here we assessed whether FXR activation may affect CAF tumor-promoting features. We showed that FXR is expressed in human CAFs isolated from four patients and treatment with the selective FXR agonist GW4064 decreased CAF migration, stress-fiber formation and contractility...
September 1, 2018: Cancer Letters
https://www.readbyqxmd.com/read/30173230/stromal-podoplanin-expression-and-its-clinicopathological-role-in-breast-carcinoma
#15
E Kumcu, H Unverdi, E Kaymaz, O Oral, D Turkbey, S Hucmenoglu
INTRODUCTION: Breast cancer is still a serious health problem in 21st century and diagnosis, treatment and prognosis of this malignant disease are subject to many research. While cancer research has been focused on tumour cells primarily, recent studies showed that tumour stroma contribute to carcinogenesis as well as tumour cells. Especially fibroblasts adjacent to epithelial tumour cells are not ordinary fibroblasts and play the critical role. Studies showed that these cancer associated fibroblasts (CAFs) have different genetic profile and protein expression...
August 2018: Malaysian Journal of Pathology
https://www.readbyqxmd.com/read/30147370/low-dose-eribulin-mesylate-exerts-antitumor-effects-in-gastric-cancer-by-inhibiting-fibrosis-via-the-suppression-of-epithelial-mesenchymal-transition-and-acts-synergistically-with-5-fluorouracil
#16
Toru Kurata, Sachio Fushida, Jun Kinoshita, Katsunobu Oyama, Takahisa Yamaguchi, Mitsuyoshi Okazaki, Tomoharu Miyashita, Hidehiro Tajima, Itasu Ninomiya, Tetsuo Ohta
Background: Characterized by aggressive proliferation, extensive stromal fibrosis, and resulting drug resistance, peritoneal dissemination in gastric cancer remains associated with poor prognosis. Interaction between cancer and stromal cells accelerates tumor progression via epithelial-mesenchymal transition (EMT), which is one of the major causes of tissue fibrosis, and human peritoneal mesothelial cells (HPMCs) play important roles as cancer stroma in peritoneal dissemination. Transforming growth factor-β (TGF-β) has a pivotal function in the progression of EMT, and Smad proteins play an important role in the TGF-β signaling pathway...
2018: Cancer Management and Research
https://www.readbyqxmd.com/read/30139956/tumour-cell-invasiveness-and-response-to-chemotherapeutics-in-adipocyte-invested-3d-engineered-anisotropic-collagen-scaffolds
#17
Robert D Hume, Sara Pensa, Elizabeth J Brown, Peter A Kreuzaler, Jessica Hitchcock, Anke Husmann, Jonathan J Campbell, Annabel O Lloyd-Thomas, Ruth E Cameron, Christine J Watson
Breast cancers are highly heterogeneous and their metastatic potential and response to therapeutic drugs is difficult to predict. A tool that could accurately gauge tumour invasiveness and drug response would provide a valuable addition to the oncologist's arsenal. We have developed a 3-dimensional (3D) culture model that recapitulates the stromal environment of breast cancers by generating anisotropic (directional) collagen scaffolds seeded with adipocytes and culturing tumour fragments therein. Analysis of tumour cell invasion in the presence of various therapeutic drugs, by immunofluorescence microscopy coupled with an optical clearing technique, demonstrated the utility of this approach in determining both the rate and capacity of tumour cells to migrate through the stroma while shedding light also on the mode of migration...
August 23, 2018: Scientific Reports
https://www.readbyqxmd.com/read/30123423/comparative-proteomics-of-soluble-factors-secreted-by-human-breast-adipose-tissue-from-tumor-and-normal-breast
#18
Sabrina Johanna Fletcher, María Belén Hapon, Eduardo A Callegari, María Luján Crosbie, Natalia Santiso, Anabela Ursino, Alicia Rita Amato, Alberto Gutiérrez, Paula Alejandra Sacca, Rubén Dreszman, Adriana Pérez, Rubén Walter Carón, Juan Carlos Calvo, Virginia Pistone-Creydt
Tumor progression depends on the tumor-stroma interaction. In the breast, adipose tissue is the predominant stromal type. We have previously demonstrated that conditioned media (CMs) from explants of human adipose tissue of tumor breasts (hATT) increase proliferation and migration of breast cancer epithelial cells when compared to human adipose tissue from normal breasts (hATN). In this work, we aim to identify specific proteins and molecular/biological pathways associated with the secretion profile of hATT and hATN explants...
July 24, 2018: Oncotarget
https://www.readbyqxmd.com/read/30119678/reawakening-of-dormant-estrogen-dependent-human-breast-cancer-cells-by-bone-marrow-stroma-secretory-senescence
#19
Samir Tivari, Haiyan Lu, Tanya Dasgupta, Mariana S De Lorenzo, Robert Wieder
BACKGROUND: Dormant estrogen receptor positive (ER+) breast cancer micrometastases in the bone marrow survive adjuvant chemotherapy and recur stochastically for more than 20 years. We hypothesized that inflammatory cytokines produced by stromal injury can re-awaken dormant breast cancer cells. METHODS: We used an established in vitro dormancy model of Michigan Cancer Foundation-7 (MCF-7) breast cancer cells incubated at clonogenic density on fibronectin-coated plates to determine the effects of inflammatory cytokines on reactivation of dormant ER+ breast cancer cells...
August 17, 2018: Cell Communication and Signaling: CCS
https://www.readbyqxmd.com/read/30119158/detection-of-the-differences-in-the-apparent-diffusion-coefficient-values-in-different-histopathological-types-of-malignant-breast-lesions-and-comparison-of-cellular-region-stroma-ratio-and-histopathological-results
#20
Nevin Köremezli Keskin, Pınar Balcı, Işıl Başara Akın, Esra Yavuz Gürkan, Ali İbrahim Sevinç, Merih Güray Durak, Ayça Erşen Danyeli
Background/aim: This study aimed to compare the apparent diffusion coefficient (ADC) values of malignant breast lesions with different histopathological types on diffusion-weighted imaging (DWI) and the cellular region/stroma (CR/S) ratio and histopathological results. Materials and methods: Breast diffusion-weighted magnetic resonance findings of 59 patients were retrospectively analyzed for malignant breast lesions. The CR/S ratio was calculated using breast wide-excisional biopsy or mastectomy specimens...
August 16, 2018: Turkish Journal of Medical Sciences
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