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https://www.readbyqxmd.com/read/27899358/cytohesin-1-regulates-homing-and-engraftment-of-human-hematopoietic-stem-and-progenitor-cells
#1
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
#2
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
#3
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
#4
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
#5
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
#6
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
#7
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)...
October 31, 2016: Autophagy
https://www.readbyqxmd.com/read/27775669/towards-stratified-medicine-in-plasma-cell-myeloma
#8
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
https://www.readbyqxmd.com/read/27750279/t-cell-acute-leukaemia-exhibits-dynamic-interactions-with-bone-marrow-microenvironments
#9
Edwin D Hawkins, Delfim Duarte, Olufolake Akinduro, Reema A Khorshed, Diana Passaro, Malgorzata Nowicka, Lenny Straszkowski, Mark K Scott, Steve Rothery, Nicola Ruivo, Katie Foster, Michaela Waibel, Ricky W Johnstone, Simon J Harrison, David A Westerman, Hang Quach, John Gribben, Mark D Robinson, Louise E Purton, Dominique Bonnet, Cristina Lo Celso
It is widely accepted that complex interactions between cancer cells and their surrounding microenvironment contribute to disease development, chemo-resistance and disease relapse. In light of this observed interdependency, novel therapeutic interventions that target specific cancer stroma cell lineages and their interactions are being sought. Here we studied a mouse model of human T-cell acute lymphoblastic leukaemia (T-ALL) and used intravital microscopy to monitor the progression of disease within the bone marrow at both the tissue-wide and single-cell level over time, from bone marrow seeding to development/selection of chemo-resistance...
October 17, 2016: Nature
https://www.readbyqxmd.com/read/27750026/gene-therapy-with-hematopoietic-stem-cells-the-diseased-bone-marrow-s-point-of-view
#10
Marina Cavazzana, Jean-Antoine Ribeil, Chantal Lagresle-Peyrou, Isabelle André-Schmutz
When considering inherited diseases that can be treated by gene transfer into hematopoietic stem cells (HSCs), there are only two in which the HSC and progenitor cell distribution inside the bone marrow and its microenvironment are exactly the same as in a healthy subject: metachromatic leukodystrophy (MLD) and adrenoleukodystrophy (ALD). In all other settings [X-linked severe combined immunodeficiency (X-SCID), adenosine deaminase deficiency, Wiskott-Aldrich syndrome, and β-hemoglobinopathies], the bone marrow content of the different stem and precursor cells and the cells' relationship with the stroma have very specific characteristics...
October 16, 2016: Stem Cells and Development
https://www.readbyqxmd.com/read/27742710/caspase-3-dependent-cleavage-of-bcl-xl-in-the-stroma-exosomes-is-required-for-their-uptake-by-hematological-malignant-cells
#11
Ioulia Vardaki, Claire Sanchez, Pedro Fonseca, Magnus Olsson, Dimitrios Chioureas, George Rassidakis, Anders Ullén, Boris Zhivotovsky, Magnus Björkholm, Theocharis Panaretakis
The intercellular crosstalk between hematological malignancies and the tumor microenvironment is mediated by cell to cell interactions and soluble factors. One component of the secretome that is gaining increasing attention are the extracellular vesicles and in particular the exosomes. Apart from the role as vectors of molecular information, exosomes have been shown to possess intrinsic biological activity. In this study we have found that caspase-3 is activated in L88 bone marrow stroma cell-derived exosomes and identified one of the substrates to be the anti-apoptotic protein Bcl-xL...
October 14, 2016: Blood
https://www.readbyqxmd.com/read/27742059/cxcl1-chemokine-c-x-c-motif-receptor-2-signaling-stimulates-the-recruitment-of-bone-marrow-derived-mesenchymal-cells-into-diffuse-type-gastric-cancer-stroma
#12
Hiroaki Kasashima, Masakazu Yashiro, Hirohisa Nakamae, Kisyu Kitayama, Go Masuda, Haruhito Kinoshita, Tatsunari Fukuoka, Tsuyoshi Hasegawa, Takahiko Nakane, Masayuki Hino, Kosei Hirakawa, Masaichi Ohira
Tumor stromal cells play a critical role in the progression of diffuse-type gastric cancer (DGC). The aim of this study was to clarify where tumor stromal cells originate from and which factor(s) recruits them into the tumor stroma. Immunodeficient mice with bone marrow transplantation from the cytomegalovirus enhancer/chicken β-actin promoter-enhanced green fluorescent protein mice were used for the in vivo experiments. An in vitro study analyzed the chemotaxis-stimulating factor from DGC cells using bone marrow-derived mesenchymal cells (BM-MCs)...
October 8, 2016: American Journal of Pathology
https://www.readbyqxmd.com/read/27738312/il27-controls-skin-tumorigenesis-via-accumulation-of-etar-positive-cd11b-cells-in-the-pre-malignant-skin
#13
Denada Dibra, Abhisek Mitra, Melissa Newman, Xueqing Xia, Camille Keenan, Jeffry J Cutrera, J Michael Mathis, Xiao-Jing Wang, Jeffrey Myers, Shulin Li
Establishment of a permissive pre-malignant niche in concert with mutant stem are key triggers to initiate skin carcinogenesis. An understudied area of research is finding upstream regulators of both these triggers. IL27, a pleiotropic cytokine with both pro- and anti-inflammatory properties, was found to be a key regulator of both. Two step skin carcinogenesis model and K15-KRASG12D mouse model were used to understand the role of IL27 in skin tumors. CD11b-/- mice and small-molecule of ETAR signaling (ZD4054) inhibitor were used in vivo to understand mechanistically how IL27 promotes skin carcinogenesis...
October 12, 2016: Oncotarget
https://www.readbyqxmd.com/read/27734833/macrophage-derived-extracellular-vesicle-packaged-wnts-rescue-intestinal-stem-cells-and-enhance-survival-after-radiation-injury
#14
Subhrajit Saha, Evelyn Aranda, Yoku Hayakawa, Payel Bhanja, Safinur Atay, N Patrik Brodin, Jiufeng Li, Samuel Asfaha, Laibin Liu, Yagnesh Tailor, Jinghang Zhang, Andrew K Godwin, Wolfgang A Tome, Timothy C Wang, Chandan Guha, Jeffrey W Pollard
WNT/β-catenin signalling is crucial for intestinal homoeostasis. The intestinal epithelium and stroma are the major source of WNT ligands but their origin and role in intestinal stem cell (ISC) and epithelial repair remains unknown. Macrophages are a major constituent of the intestinal stroma. Here, we analyse the role of macrophage-derived WNT in intestinal repair in mice by inhibiting their release using a macrophage-restricted ablation of Porcupine, a gene essential for WNT synthesis. Such Porcn-depleted mice have normal intestinal morphology but are hypersensitive to radiation injury in the intestine compared with wild-type (WT) littermates...
October 13, 2016: Nature Communications
https://www.readbyqxmd.com/read/27732933/ccr10-ccl27-crosstalk-contributes-to-failure-of-proteasome-inhibitors-in-multiple-myeloma
#15
Shanmugapriya Thangavadivel, Claudia Zelle-Rieser, Angelika Olivier, Benno Postert, Gerold Untergasser, Johann Kern, Andrea Brunner, Eberhard Gunsilius, Rainer Biedermann, Roman Hajek, Ludek Pour, Wolfgang Willenbacher, Richard Greil, Karin Jöhrer
The bone marrow microenvironment plays a decisive role in multiple myeloma progression and drug resistance. Chemokines are soluble mediators of cell migration, proliferation and survival and essentially modulate tumor progression and drug resistance. Here we investigated bone marrow-derived chemokines of naive and therapy-refractory myeloma patients and discovered that high levels of the chemokine CCL27, known so far for its role in skin inflammatory processes, correlated with worse overall survival of the patients...
October 8, 2016: Oncotarget
https://www.readbyqxmd.com/read/27730537/construction-of-thymus-organoids-from-decellularized-thymus-scaffolds
#16
Asako Tajima, Isha Pradhan, Xuehui Geng, Massimo Trucco, Yong Fan
One of the hallmarks of modern medicine is the development of therapeutics that can modulate immune responses, especially the adaptive arm of immunity, for disease intervention and prevention. While tremendous progress has been made in the past decades, manipulating the thymus, the primary lymphoid organ responsible for the development and education of T lymphocytes, remains a challenge. One of the major obstacles is the difficulty to reproduce its unique extracellular matrix (ECM) microenvironment that is essential for maintaining the function and survival of thymic epithelial cells (TECs), the predominant population of cells in the thymic stroma...
October 12, 2016: Methods in Molecular Biology
https://www.readbyqxmd.com/read/27729562/bone-marrow-stem-cell-chemotactic-activity-is-induced-by-elevated-cxcl12-in-endometriosis
#17
Irene Moridi, Ramanaiah Mamillapalli, Emine Cosar, Gulcin Sahin Ersoy, Hugh S Taylor
Endometriosis is an inflammatory gynecological disorder caused by the growth of endometrial tissue outside the uterus. Endometriosis produces chemokines, including CXCL12, that attract bone marrow cells to the lesions. In this study, we describe the expression, localization, and chemotactic activity of CXCL12 in endometriotic lesions. Biopsies were collected both from women with endometriosis undergoing laparoscopy and control endometrium from women without endometriosis. Expression of CXCl12 and CXCR4 messenger RNA was increased approximately 4- and 6-fold, respectively, in endometriosis compared to eutopic endometrium...
October 11, 2016: Reproductive Sciences
https://www.readbyqxmd.com/read/27708616/the-bone-marrow-derived-stromal-cells-commitment-and-regulation-of-adipogenesis
#18
Michaela Tencerova, Moustapha Kassem
Bone marrow (BM) microenvironment represents an important compartment of bone that regulates bone homeostasis and the balance between bone formation and bone resorption depending on the physiological needs of the organism. Abnormalities of BM microenvironmental dynamics can lead to metabolic bone diseases. BM stromal cells (also known as skeletal or mesenchymal stem cells) [bone marrow stromal stem cell (BMSC)] are multipotent stem cells located within BM stroma and give rise to osteoblasts and adipocytes. However, cellular and molecular mechanisms of BMSC lineage commitment to adipocytic lineage and regulation of BM adipocyte formation are not fully understood...
2016: Frontiers in Endocrinology
https://www.readbyqxmd.com/read/27698921/interleukin-6-from-ovarian-mesenchymal-stem-cells-promotes-proliferation-sphere-and-colony-formation-and-tumorigenesis-of-an-ovarian-cancer-cell-line-skov3
#19
Dah-Ching Ding, Hwan-Wun Liu, Tang-Yuan Chu
The origin of the majority of epithelial ovarian cancers (EOC) is regarded as extraovarian, with the ovary being the secondary site. The aim of this study was to explore the possible role of ovarian mesenchymal stem cells (OvMSCs) and secreted IL-6 in the development of EOC. OvMSCs were derived from normal ovarian stroma. Cell surface markers and differentiation capability were determined. The effects of IL-6 and conditioned medium of OvMSCs on the malignant phenotype of SKOV3 ovarian cancer cells were tested, and the status of STAT3 and ERK phosphorylation was investigated...
2016: Journal of Cancer
https://www.readbyqxmd.com/read/27643489/growth-differentiation-factor-15-contributes-to-cancer-associated-fibroblasts-mediated-chemo-protection-of-aml-cells
#20
Yuanmei Zhai, Jing Zhang, Hui Wang, Wei Lu, Sihong Liu, Yehua Yu, Wei Weng, Zhiyong Ding, Qi Zhu, Jun Shi
BACKGROUND: Chemo-resistance is still a major obstacle in efforts to overcome acute myeloid leukemia (AML). An emerging concept has proposed that interactions between the bone marrow (BM) microenvironment and leukemia cells reduce the sensitivity of the leukemia cells to chemotherapy. As an important element of the tumor microenvironment, the cancer-associated fibroblasts (CAFs) are considered to be activated modulators in the chemo-resistance of many solid tumors. But their contribution to AML has yet to be fully understood...
2016: Journal of Experimental & Clinical Cancer Research: CR
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