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bone marrow stroma

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
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 ALD. In all other settings (X-linked severe combined immunodeficiency (SCID-X1), 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 17, 2016: Stem Cells and Development
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
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
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
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
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
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
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
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
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
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
Masahiko Kanehira, Tohru Fujiwara, Shinji Nakajima, Yoko Okitsu, Yasushi Onishi, Noriko Fukuhara, Ryo Ichinohasama, Yoshinori Okada, Hideo Harigae
Mesenchymal stromal cells (MSCs) are multipotent progenitor cells and there is much interest in how MSCs contribute to the regulation of the tumor microenvironment. Whether MSCs exert a supportive or suppressive effect on tumor progression is still controversial, but is likely dependent on a variety of factors that are tumor-type dependent. Multiple myeloma (MM) is characterized by growth of malignant plasma cells in the bone marrow. It has been shown that the progression of MM is governed by MSCs, which act as a stroma of the myeloma cells...
September 19, 2016: Stem Cells
José Vázquez-Prado, Ismael Bracho-Valdés, Rodolfo Daniel Cervantes-Villagrana, Guadalupe Reyes-Cruz
Cancer cells and stroma cells in tumors secrete chemotactic agonists that exacerbate invasive behavior, promote tumor-induced angiogenesis, and recruit protumoral bone marrow-derived cells. In response to shallow gradients of chemotactic stimuli recognized by G protein-coupled receptors (GPCRs), Gβγ-dependent signaling cascades contribute to specifying the spatiotemporal assembly of cytoskeletal structures that can dynamically alter cell morphology. This sophisticated process is intrinsically linked to the activation of Rho GTPases and their cytoskeletal-remodeling effectors...
November 2016: Molecular Pharmacology
Guilherme Galvão Dos Santos, Shafqat Batool, Araceli Hastreiter, Talita Sartori, Amanda Nogueira-Pedro, Primavera Borelli, Ricardo Ambrosio Fock
Tissues that require a great supply of nutrients and possess high metabolic demands, such as lympho-hemopoietics tissues, are the first to be affected by protein malnutrition (PM). Thus, PM directly affects hemopoiesis and the production and function of immune cells. Consequently, malnourished individuals are more susceptible to infections. Mesenchymal stem cells (MSCs) have immunomodulatory properties and are important in the formation of lympho-hemopoietic stroma. Since an adequate supply of nutrients is essential to sustain stroma formation, which is mainly constituted of MSCs and differentiated cells originated from them, this study investigated whether PM would influence some biological and immunomodulatory aspects of MSCs...
August 13, 2016: Clinical Nutrition: Official Journal of the European Society of Parenteral and Enteral Nutrition
F J Vogelaar, G W van Pelt, A M van Leeuwen, J M Willems, R A E M Tollenaar, G J Liefers, W E Mesker
PURPOSE: Current TNM staging does not appropriately identify high-risk colorectal cancer (CRC) patients. The aim of this study was to evaluate whether the presence of disseminated tumor cells (DTCs) in the bone marrow (BM) and the presence of stroma in the primary tumor, i.e., the tumor-stroma ratio (TSR), in patients undergoing surgical resection of primary CRC provides information relevant for disease outcome. METHODS: Patients with primary CRC (n = 125), consecutively admitted for curative resection between 2001 and 2007, were included in the study...
September 9, 2016: Cellular Oncology (Dordrecht)
J-C Xu, G-H Wu, L-L Zhou, X-J Yang, J-T Liu
OBJECTIVE: To study the effects of leptin (LEP) on the osteogenic differentiation of human bone marrow stromal cells (hBMSCs) and to explore the mechanism controlling the process. MATERIALS AND METHODS: Respectively cultivated the third-generation hBMSCs with 100 ng/ml bone morphogenetic protein (BMP) culture media containing 320, 160, 80 and 40 ng/mL LEP, and regular medium. We administered alkaline phosphatase (ALP) dye (on the 7th day) and mineralized nodules alizarin red (on the 21st day) and tested the ALP activity as well as osteocalcin (OCN) level on 7th, 14th, 21st day in each group to establish the best inducing concentration of LEP...
August 2016: European Review for Medical and Pharmacological Sciences
Thea Kristin Våtsveen, Anne-Marit Sponaas, Erming Tian, Qing Zhang, Kristine Misund, Anders Sundan, Magne Børset, Anders Waage, Gaute Brede
BACKGROUND: Multiple myeloma is an incurable complex disease characterized by clonal proliferation of malignant plasma cells in a hypoxic bone marrow environment. Hypoxia-dependent erythropoietin (EPO)-receptor (EPOR) signaling is central in various cancers, but the relevance of EPOR signaling in multiple myeloma cells has not yet been thoroughly investigated. METHODS: Myeloma cell lines and malignant plasma cells isolated from bone marrow of myeloma patients were used in this study...
August 31, 2016: Journal of Hematology & Oncology
Esterina D'Asti, Brian Meehan, Janusz Rak
Angiogenesis represents one aspect in the complex process that leads to the generation of the vascular tumor stroma. The related functional constituents include responses of endothelial, mural, bone marrow-derived, and resident inflammatory cells as well as activation of coagulation and fibrinolytic systems in blood. Multiple molecular and cellular effectors participate in these events, often in a tumor-specific manner and with changes enforced through the microenvironment, genetic evolution, and responses to anticancer therapies...
2016: Methods in Molecular Biology
Bengi Demirayak, Nurşen Yüksel, Onur Sinan Çelik, Cansu Subaşı, Gökhan Duruksu, Z Seda Unal, Demir Kürşat Yıldız, Erdal Karaöz
In the present study, we investigate and compare the efficacy of bone marrow- and adipose tissue-derived mesenchymal stem cell (MSCs) in corneal wound healing. A penetrating injury was created in the right corneas of Wistar rats (n = 40). Ten microliters of phosphate-buffered solution (PBS) containing 2 × 10(5) green fluorescent protein (GFP) labeled bone-marrow-derived MSCs to group 1 (n = 15), 10 μl of PBS containing 2 × 10(5) GFP-labeled adipose-tissue-derived MSCs to group 2 (n = 15), 10 μl PBS was injected into anterior chamber in group 3 (n = 10, control)...
October 2016: Experimental Eye Research
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