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Breast Cancer Stroma

Ramesh Butti, Vinoth Prasanna Gunasekaran, Totakura V S Kumar, Pinaki Banerjee, Gopal C Kundu
Breast cancer remains to be a dreadful disease even with several advancements in radiation and chemotherapies, owing to the drug resistance and tumor relapse caused by breast cancer stem cells. Cancer stem cells are minute population of cells of solid tumors which show self-renewal and differentiation properties as well as tumorigenic potential. Several signaling pathways including Notch, Hippo, Wnt and Hedgehog and tumor-stroma exchanges play a critical role in the self-renewal and differentiation of cancer stem cells in breast cancer...
December 5, 2018: International Journal of Biochemistry & Cell Biology
Keiichi Takahashi
Introduction: Pleomorphic adenoma (PA) rarely originates in the mammary gland. This tumor is a benign mixed tumor and is commonly found in the salivary glands, but rarely shows findings similar to those of breast cancer. The tumor is misdiagnosed in 30-50% of the patients, including overdiagnosis of malignancy preoperatively, leading to unnecessary surgery for breast cancer. Case presentation: The present patient was a 45-year-old woman who exhibited no subjective symptoms...
December 2018: Annals of Medicine and Surgery
Ying Wang, Jia-Ning Chen, LinBin Yang, Jiaqian Li, Wei Wu, Min Huang, Ling Lin, Shicheng Su
PURPOSE: The different prognostic values of tumor-infiltrating neutrophils (TINs) in different tissue compartments are unknown. In this study, we investigated their different prognostic roles and the underlying mechanism. EXPERIMENTAL DESIGN: We evaluated CD66b+ neutrophils in primary tumors from 341 breast cancer patients from Sun Yat-Sen Memorial Hospital by immunohistochemistry. The association between stromal and parenchymal neutrophil counts and clinical outcomes was assessed in training set (170 samples), validated in internal validation set (171 samples), and further confirmed in external validation set (105 samples)...
November 27, 2018: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
Huan Cao, Melissa Kao Hui Lee, Haibo Yang, Siu Kwan Sze, Nguan Soon Tan, Chor Yong Tay
Tumor stromal residing cancer-associated fibroblasts (CAFs) are significant accomplices in the growth and development of malignant neoplasm. As cancer progresses, the stroma undergoes a dramatic remodeling and stiffening of its extracellular matrix (ECM). However, exactly how these biomechanical changes influence CAF behavior and the functional paracrine crosstalk with the neighboring tumor cells in a 3-dimensional (3D) microenvironment remains elusive. Herein, a collagen and alginate interpenetrating network (CoAl-IPN) hydrogel system was employed as a 3D in vitro surrogate of the cancerous breast tissue stromal niche...
November 27, 2018: Langmuir: the ACS Journal of Surfaces and Colloids
Jörg Kriegsmann, Mark Kriegsmann, Katharina Kriegsmann, Rémi Longuespée, Sören-Oliver Deininger, Rita Casadonte
PURPOSE: To present matrix-assisted laser desorption/ionization (MALDI) imaging as a powerful method to highlight various tissue compartments. EXPERIMENTAL DESIGN: Formalin-fixed paraffin-embedded (FFPE) tissue of a uterine cervix, a pancreas, a duodenum, a teratoma, and a breast cancer tissue microarray (TMA) are analyzed by MALDI imaging and by immunohistochemistry (IHC). Peptide images are visualized and analyzed using FlexImaging and SCiLS Lab software. Different histological compartments are compared by hierarchical cluster analysis...
November 24, 2018: Proteomics. Clinical Applications
Alison E Obr, Sushil Kumar, Yun-Juan Chang, Joseph J Bulatowicz, Betsy J Barnes, Raymond B Birge, Deborah A Lazzarino, Emily Gallagher, Derek LeRoith, Teresa L Wood
BACKGROUND: Early analyses of human breast cancer identified high expression of the insulin-like growth factor type 1 receptor (IGF-1R) correlated with hormone receptor positive breast cancer and associated with a favorable prognosis, whereas low expression of IGF-1R correlated with triple negative breast cancer (TNBC). We previously demonstrated that the IGF-1R acts as a tumor and metastasis suppressor in the Wnt1 mouse model of TNBC. The mechanisms for how reduced IGF-1R contributes to TNBC phenotypes is unknown...
November 20, 2018: Breast Cancer Research: BCR
Mieke Van Bockstal, Kathleen Lambein, Ann Smeets, Laurence Slembrouck, Patrick Neven, Ines Nevelsteen, Caroline Weltens, Erik Van Limbergen, Marie-Rose Christiaens, Chantal Van Ongeval, Hans Wildiers, Louis Libbrecht, Giuseppe Floris
BACKGROUND: Ductal carcinoma in situ (DCIS) of the breast constitutes a heterogeneous group of non-obligate precursors for invasive breast cancer. To date, adequate risk stratification is lacking, which is presumed to result in overtreatment. We previously identified myxoid stromal architecture as a potential prognosticator for loco-regional recurrence. In the present study, we investigated the prognostic potential of stromal characteristics. METHODS: Hematoxylin and eosin stained slides from 211 DCIS patients were reviewed...
November 12, 2018: European Journal of Surgical Oncology
Koji Takada, Shinichiro Kashiwagi, Wataru Goto, Yuka Asano, Katsuyuki Takahashi, Hisakazu Fujita, Tsutomu Takashima, Shuhei Tomita, Kosei Hirakawa, Masaichi Ohira
BACKGROUND: The diagnosis of metastasis by sentinel lymph node biopsy (SLNB) in early breast cancer surgery provides an accurate view of the state of metastases to the axillary lymph nodes, and it has now become the standard procedure. In the present study, whether omission of axillary lymph node dissection (ALND) after neoadjuvant chemotherapy (NAC) is possible by evaluation of tumor-infiltrating lymphocytes (TILs) before NAC in cases without metastasis on diagnostic imaging, but with metastasis on SLNB, was retrospectively investigated...
November 19, 2018: Journal of Translational Medicine
Maryse Fiche, Valentina Scabia, Patrick Aouad, Laura Battista, Assia Treboux, Athina Stravodimou, Khalil Zaman, Valerian Dormoy, Ayyakkannu Ayyanan, George Sflomos, Cathrin Brisken
Estrogen receptor α positive (ER+ ) or "luminal" breast cancers (BC) were notoriously difficult to establish as patient-derived xenografts (PDXs). We and others recently demonstrated that the microenvironment is critical for ER+ tumor cells; when grafted as single cells into milk ducts of NOD Scid gamma (NSG) females >90% of ER+ tumors can be established as xenografts and recapitulate many features of the human disease in vivo. This intra-ductal (ID) approach holds promise for personalized medicine, yet human and murine stroma are organized differently and this and other species specificities may limit the value of this model...
November 14, 2018: Journal of Pathology
Michael S Toss, Islam M Miligy, Kylie L Gorringe, L McCaffrey, Abdulbaqi AlKawaz, Asima Abidi, Ian O Ellis, Andrew R Green, Emad A Rakha
Legumain is a proteolytic enzyme that plays a role in the regulation of cell proliferation in invasive breast cancer. Studies evaluating its role in ductal carcinoma in situ (DCIS) are lacking. Here, we aimed to characterize legumain protein expression in DCIS and evaluate its prognostic significance. Legumain was assessed immunohistochemically in a tissue microarray of a well-characterized cohort of DCIS (n = 776 pure DCIS and n = 239 DCIS associated with invasive breast cancer (DCIS-mixed)). Legumain immunoreactivity was scored in tumor cells and surrounding stroma and related to clinicopathological parameters and patient outcome...
November 14, 2018: Modern Pathology: An Official Journal of the United States and Canadian Academy of Pathology, Inc
Hong Sik Park, Uiju Cho, So Young Im, Chang Young Yoo, Ji Han Jung, Oung Jin Suh, Hyun Joo Choi
Background: Human leukocyte antigen class I (HLA-I) molecules play important roles in regulating immune responses. Loss or reduction of HLA-I expression has been shown to be associated with prognosis in several cancers. Regulatory T-cells (Tregs) also play critical functions in immune response regulation. Evaluation of HLA-I expression status by the EMR8-5 antibody and its clinical impact in breast cancer have not been well studied, and its relationship with Tregs remains unclear. Materials and Methods: We evaluated HLA-I expression and Treg infiltration by immunohistochemistry in 465 surgically resected breast cancer samples...
November 14, 2018: Journal of Pathology and Translational Medicine
Jian Zhou, Shutao Zheng, Tao Liu, Qing Liu, Yumei Chen, Rong Ma, Doudou Tan, Xiaomei Lu
Although M2 tumour-associated macrophages (M2 TAMs) have been shown to be associated with the progression and metastasis of breast cancer, their role in oesophageal squamous cell carcinoma (ESCC) remains less well understood. Therefore, to understand the clinicopathological significance of infiltrated M2 TAMs in ESCC, statistical analysis was performed after immunohistochemical evaluation of CD163 expression, a well-accepted surface marker of M2 TAMs in ESCC. To gain insight into the effect of M2 TAMs, ESCC cell lines Eca109 and KYSE150 cells were co-cultured with M2 TAMs artificially induced from THP-1 cells...
November 12, 2018: Histology and Histopathology
Natasha S Clayton, Richard P Grose
Whilst cross-talk between stroma and epithelium is critical for tissue development and homeostasis, aberrant paracrine stimulation can result in neoplastic transformation. Chronic stimulation of epithelial cells with paracrine Fibroblast Growth Factor 10 (FGF10) has been implicated in multiple cancers, including breast, prostate and pancreatic ductal adenocarcinoma. Here, we examine the mechanisms underlying FGF10-induced tumourigenesis and explore novel approaches to target FGF10 signaling in cancer.
2018: Frontiers in Genetics
Marja Heiskala, Marjut Leidenius, Kristiina Joensuu, Päivi Heikkilä
Macrophages are important for the function of the innate immune system, and in solid tumors, they represent a significant proportion of the tumor mass. Tumor-associated macrophages (TAM) have a M2 phenotype and show a multitude of pro-tumoral functions, promoting tumor cell survival, proliferation, and dissemination. CCL2, synthesized by tumor and stromal cells, initiates a chemokine cascade inducing these processes. We studied by immunohistochemistry (IHC) the frequency of TAMs and CCL2 expressing cells in three groups of primary tumor (PT)-recurrence (R) pairs, where relapse was recorded within 2 years (group 1), between 5 and 10 years (group 2), and after 10 years (group 3)...
October 27, 2018: Virchows Archiv: An International Journal of Pathology
Lan G Coffman, Alexander T Pearson, Leonard G Frisbie, Zachary Freeman, Elizabeth Christie, David D Bowtell, Ronald J Buckanovich
Carcinoma-associated mesenchymal stem cells (CA-MSCs) are critical stromal progenitor cells within the tumor microenvironment (TME). We previously demonstrated that CA-MSCs differentially express bone morphogenetic protein family members, promote tumor cell growth, increase cancer "stemness," and chemotherapy resistance. Here, we use RNA sequencing of normal omental MSCs and ovarian CA-MSCs to demonstrate global changes in CA-MSC gene expression. Using these expression profiles, we create a unique predictive algorithm to classify CA-MSCs...
October 23, 2018: Stem Cells
Eleanor Broadberry, James McConnell, Jack Williams, Nan Yang, Egor Zindy, Angela Leek, Rachel Waddington, Leena Joseph, Miles Howe, Qing-Jun Meng, Charles H Streuli
BACKGROUND: Circadian rhythms maintain tissue homeostasis during the 24-h day-night cycle. Cell-autonomous circadian clocks play fundamental roles in cell division, DNA damage responses and metabolism. Circadian disruptions have been proposed as a contributing factor for cancer initiation and progression, although definitive evidence for altered molecular circadian clocks in cancer is still lacking. In this study, we looked at circadian clocks in breast cancer. METHODS: We isolated primary tumours and normal tissues from the same individuals who had developed breast cancer with no metastases...
October 22, 2018: Breast Cancer Research: BCR
Sonia Salha, Sebastian Gehmert, Vanessa Brébant, Alexandra Anker, Markus Loibl, Lukas Prantl, Sanga Gehmert
INTRODUCTION: Mesenchymal stem cells (MSCs) have been described in breast cancer models to migrate towards carcinoma and integrate into tumor associated stroma supporting tumor growth, increasing their metastatic potency and contributing to tumor-angiogenesis. Platelet-derived growth factor (PDGF) isoforms (AA, BB, CC) stimulate growth, survival and motility of MSCs and certain other cell types. Noteworthy, breast carcinomas are known to express PDGF. We aim to further shed light on i) the relevance of the different PDGF isoforms on adipose tissue derived stem cells (ASCs) migration and ii) the underlying pathway dependent on PDGF stimulation...
October 19, 2018: Clinical Hemorheology and Microcirculation
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
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
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
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