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bone marrow stroma

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https://www.readbyqxmd.com/read/28202459/il-4-cxcl12-loop-is-a-key-regulator-of-lymphoid-stroma-function-in-follicular-lymphoma
#1
Shubham Pandey, Frédéric Mourcin, Tony Marchand, Saba Nayar, Marion Guirriec, Céline Pangault, Céline Monvoisin, Patricia Amé-Thomas, Fabien Guilloton, Joelle Dulong, Mark Coles, Thierry Fest, Anja Mottok, Francesca Barone, Karin Tarte
Follicular lymphoma (FL) is the most frequent indolent lymphoma and is characterized by the accumulation of germinal center-derived malignant B cells engaged in a bidirectional crosstalk with their supportive microenvironment in invaded lymph nodes (LN) and bone marrow (BM). T follicular helper cells (TFH) and infiltrating stromal cells have been shown to favor FL B-cell growth but the mechanisms of their protumoral effect and how LN/BM microenvironment is converted into a lymphoma-permissive cell niche remain poorly understood...
February 15, 2017: Blood
https://www.readbyqxmd.com/read/28194153/nasal-polyp-derived-mesenchymal-stromal-cells-exhibit-lack-of-immune-associated-molecules-and-high-levels-of-stem-progenitor-cells-markers
#2
Pedro Wey Barbosa de Oliveira, Rogério Pezato, Juan Sebastian Henao Agudelo, Claudina Angela Perez-Novo, Wim Vanden Berghe, Niels Olsen Câmara, Danilo Candido de Almeida, Luís Carlos Gregorio
Mesenchymal stromal cells (MSCs) are considered adult progenitor stem cells and have been studied in a multitude of tissues. In this context, the microenvironment of nasal polyp tissue has several inflammatory cells, but their stroma compartment remains little elucidated. Hence, we isolated MSCs from nasal polyps Polyp-MSCs (PO-MSCs) and compared their molecular features and gene expression pattern with bone marrow-derived MSCs (BM-MSCs). Initially, both PO-MSCs and BM-MSCs were isolated, cultivated, and submitted to morphologic, differentiation, phenotypic, immunosuppressive, and gene expression assays...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28186102/cancer-cell-secreted-igf2-instigates-fibroblasts-and-bone-marrow-derived-vascular-progenitor-cells-to-promote-cancer-progression
#3
Wen Wen Xu, Bin Li, Xin Yuan Guan, Sookja K Chung, Yang Wang, Yim Ling Yip, Simon Y K Law, Kin Tak Chan, Nikki P Y Lee, Kwok Wah Chan, Li Yan Xu, En Min Li, Sai Wah Tsao, Qing-Yu He, Annie L M Cheung
Local interactions between cancer cells and stroma can produce systemic effects on distant organs to govern cancer progression. Here we show that IGF2 secreted by inhibitor of differentiation (Id1)-overexpressing oesophageal cancer cells instigates VEGFR1-positive bone marrow cells in the tumour macroenvironment to form pre-metastatic niches at distant sites by increasing VEGF secretion from cancer-associated fibroblasts. Cancer cells are then attracted to the metastatic site via the CXCL5/CXCR2 axis. Bone marrow cells transplanted from nude mice bearing Id1-overexpressing oesophageal tumours enhance tumour growth and metastasis in recipient mice, whereas systemic administration of VEGFR1 antibody abrogates these effects...
February 10, 2017: Nature Communications
https://www.readbyqxmd.com/read/28160570/resistance-of-leukemia-cells-to-cytarabine-chemotherapy-is-mediated-by-bone-marrow-stroma-involves-cell-surface-equilibrative-nucleoside-transporter-1-removal-and-correlates-with-patient-outcome
#4
Patricia Macanas-Pirard, Richard Broekhuizen, Alfonso González, Claudia Oyanadel, Daniel Ernst, Patricia García, Viviana P Montecinos, Felipe Court, Mauricio Ocqueteau, Pablo Ramirez, Bruno Nervi
The interaction between acute myeloid leukemia cells (AML) with the bone marrow stroma cells (BMSCs) determines a protective environment that favors tumor development and resistance to conventional chemotherapy. We showed that BMSCs secrete soluble factors that protect AML cells from Ara-C induced cytotoxicity. This leukemia chemoresistance is associated with a decrease in the equilibrative nucleoside transporter (ENT1) activity by inducing removal of ENT1 from the cell surface. Reduction of cell proliferation was also observed with activation of AKT and mTOR-dependent cell survival pathways, which may also contribute to the tumor chemoprotection...
February 1, 2017: Oncotarget
https://www.readbyqxmd.com/read/28158249/rb-inactivation-in-keratin-18-positive-thymic-epithelial-cells-promotes-non-cell-autonomous-t-cell-hyperproliferation-in-genetically-engineered-mice
#5
Yurong Song, Teresa Sullivan, Kimberly Klarmann, Debra Gilbert, T Norene O'Sullivan, Lucy Lu, Sophie Wang, Diana C Haines, Terry Van Dyke, Jonathan R Keller
Thymic epithelial cells (TEC), as part of thymic stroma, provide essential growth factors/cytokines and self-antigens to support T cell development and selection. Deletion of Rb family proteins in adult thymic stroma leads to T cell hyperplasia in vivo. To determine whether deletion of Rb specifically in keratin (K) 18 positive TEC was sufficient for thymocyte hyperplasia, we conditionally inactivated Rb and its family members p107 and p130 in K18+ TEC in genetically engineered mice (TgK18GT121; K18 mice). We found that thymocyte hyperproliferation was induced in mice with Rb inactivation in K18+ TEC, while normal T cell development was maintained; suggesting that inactivation of Rb specifically in K18+ TEC was sufficient and responsible for the phenotype...
2017: PloS One
https://www.readbyqxmd.com/read/28154566/histological-architecture-underlying-brain-immune-cell-cell-interactions-and-the-cerebral-response-to-systemic-inflammation
#6
Atsuyoshi Shimada, Sanae Hasegawa-Ishii
Although the brain is now known to actively interact with the immune system under non-inflammatory conditions, the site of cell-cell interactions between brain parenchymal cells and immune cells has been an open question until recently. Studies by our and other groups have indicated that brain structures such as the leptomeninges, choroid plexus stroma and epithelium, attachments of choroid plexus, vascular endothelial cells, cells of the perivascular space, circumventricular organs, and astrocytic endfeet construct the histological architecture that provides a location for intercellular interactions between bone marrow-derived myeloid lineage cells and brain parenchymal cells under non-inflammatory conditions...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28151428/bone-marrow-microenvironment-derived-signals-induce-mcl-1-dependence-in-multiple-myeloma
#7
Vikas A Gupta, Shannon M Matulis, Jason E Conage-Pough, Ajay K Nooka, Jonathan L Kaufman, Sagar Lonial, Lawrence H Boise
Multiple myeloma is highly dependent on the bone marrow microenvironment until progressing to very advanced extramedullary stages of the disease such as plasma cell leukemia. Stromal cells in the bone marrow secrete a variety of cytokines that promote plasma cell survival by regulating anti-apoptotic members of the Bcl-2 family including Mcl-1, Bcl-xL, and Bcl-2. Although the anti-apoptotic protein on which a cell depends is typically consistent amongst normal cells of a particular phenotype, Bcl-2 family dependence is highly heterogeneous in multiple myeloma...
February 1, 2017: Blood
https://www.readbyqxmd.com/read/28132882/tumor-stroma-interaction-is-mediated-by-monocarboxylate-metabolism
#8
Brijesh B Patel, Ellen Ackerstaff, Inna S Serganova, John E Kerrigan, Ronald G Blasberg, Jason A Koutcher, Debabrata Banerjee
Human breast tumors contain significant amounts of stromal cells. There exists strong evidence that these stromal cells support cancer development and progression by altering various pathways (e.g. downregulation of tumor suppressor genes or autocrine signaling loops). Here, we suggest that stromal carcinoma-associated fibroblasts (CAFs), shown to be generated from bone marrow-derived mesenchymal stem cells, may (i) recycle tumor-derived lactate for their own energetic requirements, thereby sparing glucose for neighboring glycolytic tumor cells, and (ii) subsequently secrete surplus energetically and biosynthetically valuable metabolites of lactate oxidation, such as pyruvate, to support tumor growth...
January 26, 2017: Experimental Cell Research
https://www.readbyqxmd.com/read/28114283/an-integrated-analysis-identifies-stat4-as-a-key-regulator-of-ovarian-cancer-metastasis
#9
L Zhao, G Ji, X Le, Z Luo, C Wang, M Feng, L Xu, Y Zhang, W B Lau, B Lau, Y Yang, L Lei, H Yang, Y Xuan, Y Chen, X Deng, T Yi, S Yao, X Zhao, Y Wei, S Zhou
Epithelial ovarian cancer (EOC) is one of the most common gynecological cancers, with diagnosis often at a late stage. Metastasis is a major cause of death in patients with EOC, but the underlying molecular mechanisms remain obscure. Here, we utilized an integrated approach to find potential key transcription factors involved in ovarian cancer metastasis and identified STAT4 as a critical player in ovarian cancer metastasis. We found that activated STAT4 was overexpressed in epithelial cells of ovarian cancer and STAT4 overexpression was associated with poor outcome of ovarian cancer patients, which promoted metastasis of ovarian cancer in both in vivo and in vitro...
January 23, 2017: Oncogene
https://www.readbyqxmd.com/read/28107546/bone-marrow-stroma-protects-myeloma-cells-from-cytotoxic-damage-via-induction-of-the-oncoprotein-muc1
#10
Michal Bar-Natan, Dina Stroopinsky, Katarina Luptakova, Maxwell D Coll, Arie Apel, Hasan Rajabi, Athalia R Pyzer, Kristen Palmer, Michaela R Reagan, Myrna R Nahas, Rebecca Karp Leaf, Salvia Jain, Jon Arnason, Irene M Ghobrial, Kenneth C Anderson, Donald Kufe, Jacalyn Rosenblatt, David Avigan
Multiple myeloma (MM) is a lethal haematological malignancy that arises in the context of a tumour microenvironment that promotes resistance to apoptosis and immune escape. In the present study, we demonstrate that co-culture of MM cells with stromal cells results in increased resistance to cytotoxic and biological agents as manifested by decreased rates of cell death following exposure to alkylating agents and the proteosome inhibitor, bortezomib. To identify the mechanism of increased resistance, we examined the effect of the co-culture of MM cells with stroma cells, on expression of the MUC1 oncogene, known to confer tumour cells with resistance to apoptosis and necrosis...
January 20, 2017: British Journal of Haematology
https://www.readbyqxmd.com/read/28008146/autologous-reconstitution-of-human-cancer-and-immune-system-in-vivo
#11
Juan Fu, Rupashree Sen, David L Masica, Rachel Karchin, Drew Pardoll, Vonn Walter, D Neil Hayes, Christine H Chung, Young J Kim
Correlative studies from checkpoint inhibitor trials have indicated that better understanding of human leukocytic trafficking into the human tumor microenvironment can expedite the translation of future immune-oncologic agents. In order to directly characterize signaling pathways that can regulate human leukocytic trafficking into the tumor, we have developed a completely autologous xenotransplantation method to reconstitute the human tumor immune microenvironment in vivo. We were able to genetically mark the engrafted CD34+ bone marrow cells as well as the tumor cells, and follow the endogenous leukocytic infiltration into the autologous tumor...
January 10, 2017: Oncotarget
https://www.readbyqxmd.com/read/27980223/extracellular-atp-induces-apoptosis-through-p2x7r-activation-in-acute-myeloid-leukemia-cells-but-not-in-normal-hematopoietic-stem-cells
#12
Valentina Salvestrini, Stefania Orecchioni, Giovanna Talarico, Francesca Reggiani, Cristina Mazzetti, Francesco Bertolini, Elisa Orioli, Elena Adinolfi, Francesco Di Virgilio, Annalisa Pezzi, Michele Cavo, Roberto M Lemoli, Antonio Curti
Recent studies have shown that high ATP levels exhibit direct cytotoxic effects on several cancer cells types. Among the receptors engaged by ATP, P2X7R is the most consistently expressed by tumors. P2X7R is an ATP-gated ion channel that could drive the opening of a non-selective pore, triggering cell-death signal. We previously demonstrated that acute myeloid leukemia (AML) cells express high level of P2X7R. Here, we show that P2X7R activation with high dose ATP induces AML blast cells apoptosis. Moreover, P2X7R is also expressed on leukemic stem/progenitor cells (LSCs) which are sensitive to ATP-mediated cytotoxicity...
January 24, 2017: Oncotarget
https://www.readbyqxmd.com/read/27899358/cytohesin-1-regulates-homing-and-engraftment-of-human-hematopoietic-stem-and-progenitor-cells
#13
Justyna Rak, Katie Foster, Katarzyna Potrzebowska, Mehrnaz Safaee Talkhoncheh, Natsumi Miharada, Karolina Komorowska, Therese Torngren, Anders Kvist, Åke Borg, Lena Svensson, Dominique Bonnet, Jonas Larsson
Adhesion is a key component of hematopoietic stem cell regulation mediating homing and retention to the niche in the bone marrow. Here, using an RNA interference screen, we identify cytohesin 1 (CYTH1) as a critical mediator of adhesive properties in primary human cord-blood derived hematopoietic stem and progenitor cells (HSPCs). Knockdown of CYTH1 disrupted adhesion of HSPC to primary human mesenchymal stroma cells (MSCs). Attachment to fibronectin and ICAM1, two integrin ligands, was severely impaired, and CYTH1 deficient cells showed a reduced integrin β1 activation response, suggesting that CYTH1 mediates integrin-dependent functions...
November 29, 2016: Blood
https://www.readbyqxmd.com/read/27863423/cancer-cell-ccl5-mediates-bone-marrow-independent-angiogenesis-in-breast-cancer
#14
Michael John Sax, Christin Gasch, Vineel Rag Athota, Ruth Freeman, Parisa Rasighaemi, David Elton Westcott, Christopher John Day, Iva Nikolic, Benjamin Elsworth, Ming Wei, Kelly Rogers, Alexander Swarbrick, Vivek Mittal, Normand Pouliot, Albert Sleiman Mellick
It has recently been suggested that the chemokine receptor (CCR5) is required for bone marrow (BM) derived endothelial progenitor cell (EPC) mediated angiogenesis. Here we show that suppression of either cancer cell produced CCL5, or host CCR5 leads to distinctive vascular and tumor growth defects in breast cancer. Surprisingly, CCR5 restoration in the BM alone was not sufficient to rescue the wild type phenotype, suggesting that impaired tumor growth associated with inhibiting CCL5/CCR5 is not due to defects in EPC biology...
November 16, 2016: Oncotarget
https://www.readbyqxmd.com/read/27837558/menstrual-blood-derived-stem-cells-in-vitro-and-in-vivo-characterization-of-functional-effects
#15
Maria Carolina Oliveira Rodrigues, Trenton Lippert, Hung Nguyen, Sussannah Kaelber, Paul R Sanberg, Cesar V Borlongan
Accumulating evidence has demonstrated that menstrual blood stands as a viable source of stem cells. Menstrual blood-derived stem cells (MenSCs) are morphologically and functionally similar to cells directly extracted from the endometrium, and present dual expression of mesenchymal and embryonic cell markers, thus becoming interesting tools for regenerative medicine. Functional reports show higher proliferative and self-renewal capacities than bone marrow-derived stem cells, as well as successful differentiation into hepatocyte-like cells, glial-like cells, endometrial stroma-like cells, among others...
2016: Advances in Experimental Medicine and Biology
https://www.readbyqxmd.com/read/27822872/constitutive-expression-of-inducible-cyclic-adenosine-monophosphate-early-repressor-icer-in-cycling-quiescent-hematopoietic-cells-implications-for-aging-hematopoietic-stem-cells
#16
Steven J Greco, Ghassan Yehia, Julius A Potian, Carlos A Molina, Pranela Rameshwar
Despite extensive insights on the interaction between hematopoietic stem cells (HSCs) and the supporting bone marrow (BM) stroma in hematopoietic homeostasis there remains unanswered questions on HSC regulation. We report on the mechanism by which HSCs attain cycling quiescence by addressing a role for inducible cyclic AMP early repressor (ICER). ICER negatively transcriptional regulators of cAMP activators such as CREM and CREB. These activators can be induced by hematopoietic stimulators such as cytokines...
November 8, 2016: Stem Cell Reviews
https://www.readbyqxmd.com/read/27809866/evidence-of-two-distinct-functionally-specialized-fibroblast-lineages-in-breast-stroma
#17
Mikkel Morsing, Marie Christine Klitgaard, Abbas Jafari, René Villadsen, Moustapha Kassem, Ole William Petersen, Lone Rønnov-Jessen
BACKGROUND: The terminal duct lobular unit (TDLU) is the most dynamic structure in the human breast and the putative site of origin of human breast cancer. Although stromal cells contribute to a specialized microenvironment in many organs, this component remains largely understudied in the human breast. We here demonstrate the impact on epithelium of two lineages of breast stromal fibroblasts, one of which accumulates in the TDLU while the other resides outside the TDLU in the interlobular stroma...
November 3, 2016: Breast Cancer Research: BCR
https://www.readbyqxmd.com/read/27802179/increased-phosphorylation-of-eif2%C3%AE-in-chronic-myeloid-leukemia-cells-stimulates-secretion-of-matrix-modifying-enzymes
#18
Paulina Podszywalow-Bartnicka, Anna Cmoch, Magdalena Wolczyk, Lukasz Bugajski, Marta Tkaczyk, Michal Dadlez, Margaret Nieborowska-Skorska, Antonis E Koromilas, Tomasz Skorski, Katarzyna Piwocka
Recent studies underscore the role of the microenvironment in therapy resistance of chronic myeloid leukemia (CML) cells and leukemia progression. We previously showed that sustained mild activation of endoplasmic reticulum (ER) stress in CML cells supports their survival and resistance to chemotherapy. We now demonstrate, using dominant negative non-phosphorylable mutant of eukaryotic initiation factor 2 α subunit (eIF2α), that phosphorylation of eIF2α (eIF2α-P), which is a hallmark of ER stress in CML cells, substantially enhances their invasive potential and modifies their ability to secrete extracellular components, including the matrix-modifying enzymes cathepsins and matrix metalloproteinases...
October 27, 2016: Oncotarget
https://www.readbyqxmd.com/read/27797294/targeting-autophagy-to-overcome-chemoresistance-in-acute-myleogenous-leukemia
#19
Sujan Piya, Michael Andreeff, Gautam Borthakur
Therapeutic inhibition of macroautophagy/autophagy is expected to increase chemosensitivity of cancers and alter tumor-stroma interdependence. The hypoxic, metabolically challenged bone marrow microenvironment confers chemoresistance to leukemia cells. The impact of autophagy inhibition in the context of microenvironment-mediated resistance in leukemia is less explored. Our recent studies demonstrated that co-culture of acute myelogenous leukemia (AML) cells with marrow-derived mesenchymal stromal cells (MSC) induces autophagy in AML cells and increases resistance to genotoxic agents (cytarabine and idarubicin)...
January 2, 2017: Autophagy
https://www.readbyqxmd.com/read/27775669/towards-stratified-medicine-in-plasma-cell-myeloma
#20
REVIEW
Philip Egan, Stephen Drain, Caroline Conway, Anthony J Bjourson, H Denis Alexander
Plasma cell myeloma is a clinically heterogeneous malignancy accounting for approximately one to 2% of newly diagnosed cases of cancer worldwide. Treatment options, in addition to long-established cytotoxic drugs, include autologous stem cell transplant, immune modulators, proteasome inhibitors and monoclonal antibodies, plus further targeted therapies currently in clinical trials. Whilst treatment decisions are mostly based on a patient's age, fitness, including the presence of co-morbidities, and tumour burden, significant scope exists for better risk stratification, sub-classification of disease, and predictors of response to specific therapies...
October 21, 2016: International Journal of Molecular Sciences
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