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tumor stromal microenvironment

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https://www.readbyqxmd.com/read/27926867/genomic-instability-is-induced-by-persistent-proliferation-of-cells-undergoing-epithelial-to-mesenchymal-transition
#1
Valentine Comaills, Lilian Kabeche, Robert Morris, Rémi Buisson, Min Yu, Marissa Wells Madden, Joseph A LiCausi, Myriam Boukhali, Ken Tajima, Shiwei Pan, Nicola Aceto, Srinjoy Sil, Yu Zheng, Tilak Sundaresan, Toshifumi Yae, Nicole Vincent Jordan, David T Miyamoto, David T Ting, Sridhar Ramaswamy, Wilhelm Haas, Lee Zou, Daniel A Haber, Shyamala Maheswaran
TGF-β secreted by tumor stroma induces epithelial-to-mesenchymal transition (EMT) in cancer cells, a reversible phenotype linked to cancer progression and drug resistance. However, exposure to stromal signals may also lead to heritable changes in cancer cells, which are poorly understood. We show that epithelial cells failing to undergo proliferation arrest during TGF-β-induced EMT sustain mitotic abnormalities due to failed cytokinesis, resulting in aneuploidy. This genomic instability is associated with the suppression of multiple nuclear envelope proteins implicated in mitotic regulation and is phenocopied by modulating the expression of LaminB1...
December 6, 2016: Cell Reports
https://www.readbyqxmd.com/read/27923328/modeling-stroma-induced-drug-resistance-in-a-tissue-engineered-tumor-model-of-ewing-sarcoma
#2
Marco Santoro, Brian A Menegaz, Salah-Eddine Lamhamedi-Cherradi, Eric R Molina, Danielle Wu, Waldemar Priebe, Joseph A Ludwig, Antonios G Mikos
Three-dimensional (3D) tumor models are gaining traction in the research community given their capacity to mimic aspects of the tumor microenvironment absent in monolayer systems. In particular, the ability to spatiotemporally control cell placement within ex vivo 3D systems has enabled the study of tumor-stroma interactions. Furthermore, by regulating biomechanical stimuli, one can reveal how biophysical cues affect stromal cell phenotype and how their phenotype impacts tumor drug sensitivity. Both tumor architecture and shear force have profound effects on Ewing sarcoma (ES) cell behavior and are known to elicit ligand-mediated activation of the insulin-like growth factor-1 receptor (IGF-1R), thereby mediating resistance of ES cells to IGF-1R inhibitors...
December 6, 2016: Tissue Engineering. Part A
https://www.readbyqxmd.com/read/27919940/vitamin-d-and-myofibroblasts-in-fibrosis-and-cancer-at-cross-purposes-with-tgf-%C3%AE-smad-signaling
#3
REVIEW
Shraga Shany, Ina Sigal-Batikoff, Sergio Lamprecht
The multifaceted involvement of the active vitamin D metabolite 1,25-dihydroxyvitamin D3 (henceforth referred to by the synonyms 1,25(OH)2D3, calcitriol or vitamin D) in blunting the growth of cancer cells is amply recognized. In this review we focused our attention on the cross-talk between 1,25 (OH)2D3 and the tumor microenvironment (TME), signaling out stromal cancer-associated fibroblasts (CAFs), the most abundant TME population, as a target for calcitriol anticancer action. In view of the commonality of the phenotypic signature in myofibroblasts, resident in the cancer stroma and in non-neoplastic fibrotic loci, we examined modes of action of vitamin D in non-neoplastic chronic diseases and in cancer to assess mechanistic similarities and divergences...
December 2016: Anticancer Research
https://www.readbyqxmd.com/read/27919908/targeting-the-pd-1-pd-l1-axis-in-multiple-myeloma-a-dream-or-a-reality
#4
Jacalyn Rosenblatt, David Avigan
PD-1/PD-L1 pathway is a negative regulator of immune activation that is up-regulated in multiple myeloma and is a critical component of the immunosuppressive tumor microenvironment. Expression is increased in advanced disease and in the presence of bone marrow stromal cells. PD-1/PD-L1 blockade is associated with tumor regression in several malignancies but single agent activity is limited in myeloma patients. Combination therapy involving strategies to expand myeloma specific T cells and T cell activation via PD-1/PD-L1 blockade are currently being explored...
December 5, 2016: Blood
https://www.readbyqxmd.com/read/27916739/bioengineered-tumoral-microtissues-recapitulate-desmoplastic-reaction-of-pancreatic-cancer
#5
Virginia Brancato, Valentina Comunanza, Giorgia Imparato, Davide Corà, Francesco Urciuolo, Alessio Noghero, Federico Bussolino, Paolo A Netti
: Many of the existing three-dimensional (3D) cancer models in vitro fail to represent the entire complex tumor microenvironment composed of cells and extra cellular matrix (ECM) and do not allow a reliable study of the tumoral features and progression. In this paper we reported a strategy to produce 3D in vitro microtissues of pancreatic ductal adenocarcinoma (PDAC) for studying the desmoplastic reaction activated by the stroma-cancer crosstalk. Human PDAC microtissues were obtained by co-culturing pancreatic cancer cells (PT45) and normal or cancer-associated fibroblasts within biodegradable microcarriers in a spinner flask bioreactor...
December 1, 2016: Acta Biomaterialia
https://www.readbyqxmd.com/read/27914452/inflammatory-immune-infiltration-in-human-tumors-role-in-pathogenesis-and-prognostic-and-diagnostic-value
#6
REVIEW
A V Bogolyubova, P V Belousov
The cellular microenvironment directly and indirectly influences tumor development and possesses prognostic and in some cases diagnostic value. Over the years, understanding of structural organization of the immune/inflammatory moiety of neoplasms as well as in-depth phenotypic and transcriptomic profiling of its cellular components together provide more and more insights in both basic and translational medical science. In this review, we will discuss the specific roles of various stromal cells and their impact on neoplastic progression as well as address the use of quantitative and phenotypic analysis of immune/inflammatory infiltrate for diagnostics and predicting the clinical course of human malignancies...
November 2016: Biochemistry. Biokhimii︠a︡
https://www.readbyqxmd.com/read/27914000/from-transformation-to-metastasis-deconstructing-the-extracellular-matrix-in-breast-cancer
#7
Shelly Kaushik, Michael W Pickup, Valerie M Weaver
The extracellular matrix (ECM) is a guiding force that regulates various developmental stages of the breast. In addition to providing structural support for the cells, it mediates epithelial-stromal communication and provides cues for cell survival, proliferation, and differentiation. Perturbations in ECM architecture profoundly influence breast tumor progression and metastasis. Understanding how a dysregulated ECM can facilitate malignant transformation is crucial to designing treatments to effectively target the tumor microenvironment...
December 2, 2016: Cancer Metastasis Reviews
https://www.readbyqxmd.com/read/27912781/an-immune-stratification-reveals-a-subset-of-pd-1-lag-3-double-positive-triple-negative-breast-cancers
#8
Giulia Bottai, Carlotta Raschioni, Agnese Losurdo, Luca Di Tommaso, Corrado Tinterri, Rosalba Torrisi, Jorge S Reis-Filho, Massimo Roncalli, Christos Sotiriou, Armando Santoro, Alberto Mantovani, Sherene Loi, Libero Santarpia
BACKGROUND: Stromal tumor-infiltrating lymphocytes (TILs) are a robust prognostic factor in triple-negative breast cancer (TNBC). However, the clinical significance of TILs may be influenced by the complex landscape of the tumor immune microenvironment. In this study, we aimed to evaluate the composition and the functionality of lymphocytic infiltration and checkpoint receptors in TNBC. METHODS: Formalin-fixed, paraffin-embedded tissues were retrospectively collected from a cohort of patients with early-stage TNBC treated with adjuvant anthracycline-based chemotherapy (n = 259)...
December 3, 2016: Breast Cancer Research: BCR
https://www.readbyqxmd.com/read/27909407/the-tlr4-active-morphine-metabolite-morphine-3-glucuronide-does-not-elicit-macrophage-classical-activation-in-vitro
#9
Samira Khabbazi, Nan Xie, Wenjun Pu, Yannick Goumon, Marie-Odile Parat
Macrophages are abundant in the tumor microenvironment where they adopt a pro-tumor phenotype following alternative polarization induced by paracrine factors from cancer and stromal cells. In contrast, classically activated macrophages have tumoricidal activities, such that the polarization of tumor-associated macrophages has become a novel therapeutic target. Toll-like receptor 4 engagement promotes classical activation of macrophages, and recent literature suggests TLR4 agonism to prevent metastasis and promote survival in experimental metastasis models...
2016: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/27904036/differential-regulation-of-lympho-myelopoiesis-by-stromal-cells-in-the-early-and-late-phases-in-balb-c-mice-repeatedly-exposed-to-lipopolysaccharide
#10
Isao Tsuboi, Tomonori Harada, Yoko Hirabayashi, Jun Kanno, Shin Aizawa
Chronic lipopolysaccharide (LPS) exposure to mice reduces the lymphoid compartment and skews the hematopoietic cell compartment toward myeloid-cells, which is considered to be a direct effect of LPS on hematopoietic stem cells. However, the effect of chronic LPS exposure on stromal-cells, which compose the hematopoietic microenvironment, has not been elucidated. Here, we investigated early- and late-phase effects of repeated LPS exposure on stromal-cells. During the early phase, when mice were treated with 5 or 25 µg LPS three times at weekly intervals, the numbers of myeloid-progenitor (colony forming unit-granulocyte macrophage (CFU-GM)) cells and B lymphoid-progenitor (CFU-preB) cells in the bone-marrow (BM) rapidly decreased after each treatment...
2016: Biological & Pharmaceutical Bulletin
https://www.readbyqxmd.com/read/27899994/targeting-of-the-leukemia-microenvironment-by-c-rgdfv-overcomes-the-resistance-to-chemotherapy-in-acute-myeloid-leukemia-in-biomimetic-polystyrene-scaffolds
#11
Zhao-Hua Shen, Dong-Feng Zeng, Xiao-Yan Wang, Ying-Ying Ma, Xi Zhang, Pei-Yan Kong
The bone marrow microenvironment provides a relative sanctuary from cytotoxic drugs for leukemia cells. The present niche models concentrate on a two-dimensional (2D) co-culture system in vitro, which does not imitate the in vivo environment, while the 3D scaffolds are more reflective of this. Osteopontin (Opn) secreted by bone marrow osteoblasts, may participate in protecting leukemia cells from apoptosis by binding to its receptor αvβ3, which can be expressed on the surface of the leukemia MV4-11 cell line...
November 2016: Oncology Letters
https://www.readbyqxmd.com/read/27896643/a-novel-signaling-role-for-mir-451-in-esophageal-tumor-microenvironment-and-its-contribution-to-tumor-progression
#12
S Khazaei, N Nouraee, A Moradi, S J Mowla
OBJECTIVE: We evaluated miR-451 expression in serum and tissue samples of esophageal squamous cell carcinoma (ESCC) patients. Then, we examined a secretory role of miR-451 in esophageal tumor microenvironment. METHODS: miR-451 expression was evaluated in 39 serum samples from esophageal SCC patients compared to 39 normal individuals as well as 26 pairs of fresh-frozen tumor and adjacent normal tissues from patients with ESCC, using qRT-PCR. In a co-culture system of human normal fibroblasts (HFSF-PI3) and esophageal cancer cell line (KYSE-30), we evaluated exosomal miR-451 secretion into the conditioned medium (CM) of both cell lines...
November 28, 2016: Clinical & Translational Oncology
https://www.readbyqxmd.com/read/27896217/adapt-recycle-and-move-on-proteostasis-and-trafficking-mechanisms-in-melanoma
#13
REVIEW
Seyma Demirsoy, Shaun Martin, Hannelore Maes, Patrizia Agostinis
Melanoma has emerged as a paradigm of a highly aggressive and plastic cancer, capable to co-opt the tumor stroma in order to adapt to the hostile microenvironment, suppress immunosurveillance mechanisms, and disseminate. In particular, oncogene- and aneuploidy-driven dysregulations of proteostasis in melanoma cells impose a rewiring of central proteostatic processes, such as the heat shock and unfolded protein responses, autophagy, and the endo-lysosomal system, to avoid proteotoxicity. Research over the past decade has indicated that alterations in key nodes of these proteostasis pathways act in conjunction with crucial oncogenic drivers to increase intrinsic adaptations of melanoma cells against proteotoxic stress, modulate the high metabolic demand of these cancer cells and the interface with other stromal cells, through the heightened release of soluble factors or exosomes...
2016: Frontiers in Oncology
https://www.readbyqxmd.com/read/27895734/periostin-and-tumor-stroma-interactions-in-non-small-cell-lung-cancer
#14
Ulrich Nitsche, Daniela Stangel, Zheng Pan, Anna Melissa Schlitter, Irene Esposito, Ivonne Regel, Susanne Raulefs, Helmut Friess, Jörg Kleeff, Mert Erkan
Non-small cell lung cancer (NSCLC) is one of the leading causes of cancer-associated mortality globally. Interactions of the cancer cells with the tumor microenvironment are essential carcinogenic features for the majority of solid tumors, such as pancreatic cancer. The present study investigated the role of stromal activation in NSCLC and analyzed the surgical specimens of 93 patients by immunohistochemistry with regard to periostin (an extracellular matrix protein), α-smooth muscle actin (α-SMA; a marker of myofibroblasts) and cluster of differentiation 31 (CD31; a marker of endothelial cells), and the activated stroma index...
November 2016: Oncology Letters
https://www.readbyqxmd.com/read/27890927/the-ap-1-transcription-factor-junb-is-essential-for-multiple-myeloma-cell-proliferation-and-drug-resistance-in-the-bone-marrow-microenvironment
#15
F Fan, M H Bashari, E Morelli, G Tonon, S Malvestiti, S Vallet, M Jarahian, A Seckinger, D Hose, L Bakiri, C Sun, Y Hu, C R Ball, H Glimm, M Sattler, H Goldschmidt, E F Wagner, P Tassone, D Jaeger, K Podar
Despite therapeutic advances, multiple myeloma (MM) remains an incurable disease, predominantly due to the development of drug resistance. The activator protein-1 (AP-1) transcription factor family has been implicated in a multitude of physiologic processes and tumorigenesis; however, its role in MM is largely unknown. Here we demonstrate specific and rapid induction of the AP-1 family member JunB in MM cells when co-cultured with bone marrow stromal cells. Supporting a functional key role of JunB in MM pathogenesis, knockdown of JUNB significantly inhibited in vitro MM cell proliferation and survival...
November 28, 2016: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/27888521/cancer-associated-mesenchymal-stroma-fosters-the-stemness-of-osteosarcoma-cells-in-response-to-intratumoral-acidosis-via-nf-%C3%AE%C2%BAb-acivation
#16
Sofia Avnet, Gemma Di Pompo, Tokuhiro Chano, Costantino Errani, Arig Ibrahim-Hashim, Robert J Gillies, Davide Maria Donati, Nicola Baldini
The role of mesenchymal stem cells (MSC) in osteosarcoma (OS), the most common primary tumor of bone, has not been extensively elucidated. We have recently shown that OS is characterized by interstitial acidosis, a microenvironmental condition that is similar to a wound setting, in which mesenchymal reactive cells are activated to release mitogenic and chemotactic factors. We therefore intended to test the hypothesis that, in OS, acid-activated MSC influence tumor cell behavior. Conditioned media or co-culture with normal MSC previously incubated with short-term acidosis (pH 6...
November 26, 2016: International Journal of Cancer. Journal International du Cancer
https://www.readbyqxmd.com/read/27887656/looking-beyond-the-cancer-cell-for-effective-drug-combinations
#17
Jonathan R Dry, Mi Yang, Julio Saez-Rodriguez
Combinations of therapies are being actively pursued to expand therapeutic options and deal with cancer's pervasive resistance to treatment. Research efforts to discover effective combination treatments have focused on drugs targeting intracellular processes of the cancer cells and in particular on small molecules that target aberrant kinases. Accordingly, most of the computational methods used to study, predict, and develop drug combinations concentrate on these modes of action and signaling processes within the cancer cell...
November 25, 2016: Genome Medicine
https://www.readbyqxmd.com/read/27868286/a-high-number-of-stromal-tumor-infiltrating-lymphocytes-is-a-favorable-independent-prognostic-factor-in-m0-stages-i-iii-esophageal-squamous-cell-carcinoma
#18
Jing Li, Yang Tang, Liu Huang, Qianqian Yu, Guangyuan Hu, Yanmei Zou, Xianglin Yuan
Esophageal cancer is a highly invasive tumor with a poor prognosis. Lymphocytes play an important role in systemic immune responses, but their role in cancers varies depending on the specific tumor microenvironment. The aim of this study was to provide evidence for tumor-infiltrating lymphocytes (TILs) as a prognostic biomarker in esophageal squamous cell carcinoma. TIL analysis was retrospectively performed on full-face hematoxylin and eosin-stained sections from 127 patients. A majority (92.6%) of tumors had at least 10% stromal TILs (sTILs) (range, 10%-90%), and 84...
November 21, 2016: Diseases of the Esophagus: Official Journal of the International Society for Diseases of the Esophagus
https://www.readbyqxmd.com/read/27868214/low-intratumoral-mast-cells-are-associated-with-a-higher-risk-of-prostate-cancer-recurrence
#19
Heidi A Hempel, Nathan S Cuka, Ibrahim Kulac, John R Barber, Toby C Cornish, Elizabeth A Platz, Angelo M De Marzo, Karen S Sfanos
BACKGROUND: Mast cells are of interest in prostate cancer because they possess both pro- and anti-tumorigenic properties and are present in the tumor microenvironment. We studied the association of mast cell count and densities with prostate cancer recurrence using tissue microarrays (TMAs) for 462 men who recurred (cases) and 462 controls that were matched to the cases nested in a cohort of radical prostatectomy patients. METHODS: Dual-immunostaining for mast cell tryptase and epithelial cytokeratin-8 and whole slide image analysis were used to assess total mast cell number, mast cell density (mast cell number/tissue area), and mast cell number per epithelial or stromal area in TMA spots containing tumor (up to 4 per man)...
November 21, 2016: Prostate
https://www.readbyqxmd.com/read/27865458/the-interaction-between-human-papillomaviruses-and-the-stromal-microenvironment
#20
B Woodby, M Scott, J Bodily
Human papillomaviruses (HPVs) are small, double-stranded DNA viruses that replicate in stratified squamous epithelia and cause a variety of malignancies. Current efforts in HPV biology are focused on understanding the virus-host interactions that enable HPV to persist for years or decades in the tissue. The importance of interactions between tumor cells and the stromal microenvironment has become increasingly apparent in recent years, but how stromal interactions impact the normal, benign life cycle of HPVs, or progression of lesions to cancer is less understood...
2016: Progress in Molecular Biology and Translational Science
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