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Bone marrow microenvironment

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https://www.readbyqxmd.com/read/29138883/hallmarks-of-bone-metastasis
#1
REVIEW
Rachelle W Johnson, Larry J Suva
Breast cancer bone metastasis develops as the result of a series of complex interactions between tumor cells, bone marrow cells, and resident bone cells. The net effect of these interactions are the disruption of normal bone homeostasis, often with significantly increased osteoclast and osteoblast activity, which has provided a rational target for controlling tumor progression, with little or no emphasis on tumor eradication. Indeed, the clinical course of metastatic breast cancer is relatively long, with patients likely to experience sequential skeletal-related events (SREs), often over lengthy periods of time, even up to decades...
November 14, 2017: Calcified Tissue International
https://www.readbyqxmd.com/read/29138574/cancer-cell-dormancy-mechanisms-and-implications-of-cancer-recurrence-and-metastasis
#2
REVIEW
Xiao-Lei Gao, Mei Zhang, Ya-Ling Tang, Xin-Hua Liang
More recently, disease metastasis and relapse in many cancer patients several years (even some decades) after surgical remission are regarded as tumor dormancy. However, the knowledge of this phenomenon is cripplingly limited. Substantial quantities of reviews have summarized three main potential models that can be put forth to explain such process, including angiogenic dormancy, immunologic dormancy, and cellular dormancy. In this review, newly uncovered mechanisms governing cancer cell dormancy are discussed, with an emphasis on the cross talk between dormant cancer cells and their microenvironments...
2017: OncoTargets and Therapy
https://www.readbyqxmd.com/read/29138545/activation-of-notch1-signaling-alleviates-dysfunction-of-bone-marrow-derived-mesenchymal-stem-cells-induced-by-cigarette-smoke-extract
#3
Yi Cheng, Wen Gu, Guorui Zhang, Xiaoming Li, Xuejun Guo
Bone marrow-derived mesenchymal stem cells (BM-MSCs) are considered attractive therapeutic agents for the treatment of COPD. However, little is known about the impact of Notch on the proliferation, migration, and survival of MSCs in a cigarette smoke (CS) microenvironment. Here, we used CS extract to mimic the CS microenvironment in vitro, with the intention to investigate the effect of Notch in regulating proliferation, migration, and survival of BM-MSCs. Rat bone marrow mesenchymal stem cells were infected with lentivirus vector containing the intracellular domain of Notch1 (N1ICD) and challenged with CS extract...
2017: International Journal of Chronic Obstructive Pulmonary Disease
https://www.readbyqxmd.com/read/29137349/tumor-trp53-status-and-genotype-affect-the-bone-marrow-microenvironment-in-acute-myeloid-leukemia
#4
Rodrigo Jacamo, R Eric Davis, Xiaoyang Ling, Sonali Sonnylal, Zhiqiang Wang, Wencai Ma, Min Zhang, Peter Ruvolo, Vivian Ruvolo, Rui-Yu Wang, Teresa McQueen, Scott Lowe, Johannes Zuber, Steven M Kornblau, Marina Konopleva, Michael Andreeff
The genetic heterogeneity of acute myeloid leukemia (AML) and the variable responses of individual patients to therapy suggest that different AML genotypes may influence the bone marrow (BM) microenvironment in different ways. We performed gene expression profiling of bone marrow mesenchymal stromal cells (BM-MSC) isolated from normal C57BL/6 mice or mice inoculated with syngeneic murine leukemia cells carrying different human AML genotypes, developed in mice with Trp53 wild-type or nullgenetic backgrounds...
October 13, 2017: Oncotarget
https://www.readbyqxmd.com/read/29137304/monocarboxylate-transporter-1-mct1-a-tool-to-stratify-acute-myeloid-leukemia-aml-patients-and-a-vehicle-to-kill-cancer-cells
#5
Filipa Lopes-Coelho, Carolina Nunes, Sofia Gouveia-Fernandes, Rita Rosas, Fernanda Silva, Paula Gameiro, Tânia Carvalho, Maria Gomes da Silva, José Cabeçadas, Sérgio Dias, Luís G Gonçalves, Jacinta Serpa
Dysregulation of glucose/lactate dynamics plays a role in cancer progression, and MCTs are key elements in metabolic remodeling. VEGF is a relevant growth factor in the maintenance of bone marrow microenvironment and it is also important in hematological diseases. Our aim was to investigate the role of VEGF in the metabolic adaptation of Acute myeloid leukemia (AML) cells by evaluating the metabolic profiles and cell features according to the AML lineage and testing lactate as a metabolic coin. Our in vitro results showed that AML promyelocytic (HL60) and monocytic (THP1) (but not erythroid- HEL) lineages are well adapted to VEGF and lactate rich environment...
October 10, 2017: Oncotarget
https://www.readbyqxmd.com/read/29137220/stromal-cyclin-d1-promotes-heterotypic-immune-signaling-and-breast-cancer-growth
#6
Timothy G Pestell, Xuanmao Jiao, Mukesh Kumar, Amy R Peck, Marco Prisco, Shengqiong Deng, Zhiping Li, Adam Ertel, Mathew C Casimiro, Xiaoming Ju, Agnese Di Rocco, Gabriele Di Sante, Sanjay Katiyar, Alison Shupp, Michael P Lisanti, Pooja Jain, Kongming Wu, Hallgeir Rui, Douglas C Hooper, Zuoren Yu, Aaron R Goldman, David W Speicher, Lisa Laury-Kleintop, Richard G Pestell
The cyclin D1 gene encodes the regulatory subunit of a holoenzyme that drives cell autonomous cell cycle progression and proliferation. Herein we show cyclin D1 abundance is increased >30-fold in the stromal fibroblasts of patients with invasive breast cancer, associated with poor outcome. Cyclin D1 transformed hTERT human fibroblast to a cancer-associated fibroblast phenotype. Stromal fibroblast expression of cyclin D1 (cyclin D1(Stroma)) in vivo, enhanced breast epithelial cancer tumor growth, restrained apoptosis, and increased autophagy...
October 10, 2017: Oncotarget
https://www.readbyqxmd.com/read/29136112/local-production-of-tenascin-c-acts-as-a-trigger-for-monocyte-macrophage-recruitment-that-provokes-cardiac-dysfunction
#7
Dounia Abbadi, Fanny Laroumanie, Mathilde Bizou, Joffrey Pozzo, Danièle Daviaud, Christine Delage, Denis Calise, Fréderique Gaits-Iacovoni, Marianne Dutaur, Florence Tortosa, Edith Renaud-Gabardos, Victorine Douin-Echinard, Anne-Catherine Prats, Jerome Roncalli, Angelo Parini, Nathalie Pizzinat
Aims: Tenascin-C (TNC) is an endogenous danger signal molecule strongly associated with inflammatory diseases and with poor outcome in patients with cardiomyopathies. Its function within pathological cardiac tissue during pressure overload remains poorly understood. Methods and results: We showed that TNC accumulates after 1 week of transverse aortic constriction (TAC) in the heart of 12-week-old male mice. By cross bone marrow transplantation experiments, we determined that TNC deposition relied on cardiac cells and not on haematopoietic cells...
November 10, 2017: Cardiovascular Research
https://www.readbyqxmd.com/read/29131149/three-dimensional-map-of-nonhematopoietic-bone-and-bone-marrow-cells-and-molecules
#8
Daniel L Coutu, Konstantinos D Kokkaliaris, Leo Kunz, Timm Schroeder
The bone marrow (BM) microenvironment contains many types of cells and molecules with roles in hematopoiesis, osteogenesis, angiogenesis and metabolism. The spatial distribution of the different bone and BM cell types remains elusive, owing to technical challenges associated with bone imaging. To map nonhematopoietic cells and structures in bone and BM, we performed multicolor 3D imaging of osteoblastic, vascular, perivascular, neuronal and marrow stromal cells, and extracellular-matrix proteins in whole mouse femurs...
November 13, 2017: Nature Biotechnology
https://www.readbyqxmd.com/read/29129292/targeting-myeloid-cells-in-the-tumor-sustaining-microenvironment
#9
REVIEW
Jonathan Schupp, Franziska K Krebs, Niklas Zimmer, Emily Trzeciak, Detlef Schuppan, Andrea Tuettenberg
Myeloid cells are the most abundant cells in the tumor microenvironment (TME). The tumor recruits and modulates endogenous myeloid cells to tumor-associated macrophages (TAM), dendritic cells (DC), myeloid-derived suppressor cells (MDSC) and neutrophils (TAN), to sustain an immunosuppressive environment. Pathologically overexpressed mediators produced by cancer cells like granulocyte-macrophage colony-stimulating- and vascular endothelial growth factor induce myelopoiesis in the bone marrow. Excess of myeloid cells in the blood, periphery and tumor has been associated with tumor burden...
November 2, 2017: Cellular Immunology
https://www.readbyqxmd.com/read/29122993/the-microenvironmental-stromal-cells-abrogate-nf-%C3%AE%C2%BAb-inhibitor-induced-apoptosis-in-chronic-lymphocytic-leukemia
#10
Carl Philipp Simon-Gabriel, Katharina Foerster, Shifa Saleem, Dorothee Bleckmann, Marco Benkisser-Petersen, Nicolas Thornton, Kazuo Umezawa, Sarah Decker, Meike Burger, Hendrik Veelken, Rainer Claus, Christine Dierks, Justus Duyster, Katja Zirlik
NF-κB is known to play an important role in the pathogenesis of chronic lymphocytic leukemia. Several NF-κB inhibitors have been shown to successfully induce apoptosis of chronic lymphocytic leukemia cells in vitro. Since the microenvironment is known to be crucial for the survival of chronic lymphocytic leukemia cells, we tested here whether NF-κB inhibition may still induce apoptosis in these leukemic cells in the presence of protective stromal interaction. We used the specific NF-κB inhibitor Dehydroxymethylepoxyquinomicin...
November 9, 2017: Haematologica
https://www.readbyqxmd.com/read/29120093/imbalanced-osteogenesis-and-adipogenesis-in-mice-deficient-of-the-chemokine-cxcl12-sdf1-in-the-bone-mesenchymal-stem-progenitor-cells
#11
Yi-Shiuan Tzeng, Ni-Chun Chung, Yu-Ren Chen, Hsin-Yi Huang, Wen-Po Chunang, Dar-Ming Lai
Bone and bone marrow serve as an imperative ecosystem to various types of cells participating in critical body functions. The chemokine Cxcl12, also known as stromal cell-derived factor 1 (Sdf1), is one of the communication factors in the marrow microenvironment that regulate hematopoietic stem/progenitor cell homeostasis. However, the function of Cxcl12 in other bone marrow cells in vivo is yet to be discovered. Here we report a novel function of Cxcl12 in postnatal bone development and homeostasis. Targeted deletion of Cxcl12 in Prx1- or Osx-expressing mesenchymal stem/progenitor cells (MSPCs), but not in mature osteoblasts, resulted in marrow adiposity and reduced trabecular bone content...
November 9, 2017: Journal of Bone and Mineral Research: the Official Journal of the American Society for Bone and Mineral Research
https://www.readbyqxmd.com/read/29120053/tumor-conditions-induce-bone-marrow-expansion-of-granulocytic-but-not-monocytic-immunosuppressive-leukocytes-with-increased-cxcr2-expression-in-mice
#12
Zhen Bian, Lei Shi, Mahathi Venkataramani, Ahmed Mansour Abdelaal, Courtney Culpepper, Koby Kidder, Hongwei Liang, Ke Zen, Yuan Liu
Myeloid-derived suppressor cells (MDSCs) promote tumor growth through, in part, inhibiting T cell immunity. However, mechanisms underlying MDSC expansion and guidance of MDSCs toward the tumor microenvironment remain unclear. Employing Percoll density gradients, we separate bone marrow (BM) leukocytes from tumor-bearing mice into four density-increasing bands with myeloid leukocytes enriched in bands III and IV. Band III comprises monocytes and low-density granulocytes, both confirmed to be M-MDSCs and G-MDSCs, respectively, by displaying potent inhibition of T cell proliferation...
November 9, 2017: European Journal of Immunology
https://www.readbyqxmd.com/read/29119288/renal-macrophages-and-dendritic-cells-in-sle-nephritis
#13
REVIEW
Naomi I Maria, Anne Davidson
PURPOSE OF REVIEW: The purpose of the study was to review the characteristics of renal macrophages and dendritic cells during homeostasis and disease, with a particular focus on lupus nephritis. RECENT FINDINGS: Resident renal macrophages derive from embryonic sources and are long-lived and self-renewing; they are also replaced from the bone marrow with age. The unique characteristics of macrophages in each tissue are imposed by the microenvironment and reinforced by epigenetic modifications...
November 9, 2017: Current Rheumatology Reports
https://www.readbyqxmd.com/read/29116018/tissue-specific-role-of-rhbdf2-in-cutaneous-wound-healing-and-hyperproliferative-skin-disease
#14
Vishnu Hosur, Bonnie L Lyons, Lisa M Burzenski, Leonard D Shultz
OBJECTIVE: Gain-of-function (GOF) mutations in RHBDF2 cause tylosis. Patients present with hyperproliferative skin, and keratinocytes from tylosis patients' skin show an enhanced wound-healing phenotype. The curly bare mouse model of tylosis, carrying a GOF mutation in the Rhbdf2 gene (Rhbdf2 (cub) ), presents with epidermal hyperplasia and shows accelerated cutaneous wound-healing phenotype through enhanced secretion of the epidermal growth factor receptor family ligand amphiregulin...
November 7, 2017: BMC Research Notes
https://www.readbyqxmd.com/read/29115987/cancer-cell-soluble-factors-reprogram-mesenchymal-stromal-cells-to-slow-cycling-chemoresistant-cells-with-a-more-stem-like-state
#15
Ahmed El-Badawy, Mohamed A Ghoneim, Mahmoud M Gabr, Radwa Ayman Salah, Ihab K Mohamed, Marwa Amer, Nagwa El-Badri
BACKGROUND: Mesenchymal stem cells (MSCs) play different roles in modulating tumor progression, growth, and metastasis. MSCs are recruited to the tumor site in large numbers and subsequently have an important microenvironmental role in modulating tumor progression and drug sensitivity. However, the effect of the tumor microenvironment on MSC plasticity remains poorly understood. Herein, we report a paracrine effect of cancer cells, in which they secrete soluble factors that promote a more stem-like state in bone marrow mesenchymal stem cells (BM-MSCs)...
November 7, 2017: Stem Cell Research & Therapy
https://www.readbyqxmd.com/read/29115630/tipe2-governs-macrophage-polarization-via-negative-regulation-of-mtorc1
#16
Yuan Jiang, Qiang Li, Yuanyuan Zhang, Yuzhi Gao, Libing Jiang, Zhimin Chen
Macrophages can be polarized into the inflammatory M1 lineage or the immunomodulatory M2 lineage, depending on the differential tissue microenvironment signaling, specific pathogens or cytokine stimulation. Tumor necrosis factor α‑induced protein 8‑like protein 2 (TIPE2) has been demonstrated to negatively regulate inflammation by inhibiting the Toll‑like receptor (TLR) pathway. The present study utilized murine bone marrow derived macrophages (BMDMs) as the model of undifferentiated (M0) macrophages to study the roles of TIPE2 in the differential polarization status of BMDMs...
November 6, 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/29113449/where-hematopoietic-stem-cells-live-the-bone-marrow-niche
#17
Krzysztof Tomasz Szade, Gunsagar Singh Gulati, Charles K F Chan, Kevin S Kao, Masanori Miyanishi, Kristopher Marjon, Rahul Sinha, Benson George, James Y Chen, Irving Weissman
Hematopoietic stem cells (HSCs) can sustain the production of blood throughout one's lifetime. However, for proper self-renewal of its own population and differentiation to blood, the HSC requires a specialized microenvironment called the "niche". Recent Advances: Recent studies using novel mouse models have shed new light on the cellular architecture and function of the HSC niche. Here, we review the different cells that constitute the HSC niche and the molecular mechanisms that underlie HSC and niche interaction...
November 7, 2017: Antioxidants & Redox Signaling
https://www.readbyqxmd.com/read/29113298/il-8-gro-and-mcp-1-produced-by-hepatocellular-carcinoma-microenvironment-determine-the-migratory-capacity-of-human-bone-marrow-derived-mesenchymal-stromal-cells-without-affecting-tumor-aggressiveness
#18
Juan Bayo, Alejandrina Real, Esteban J Fiore, Mariana Malvicini, Leonardo Sganga, Marcela Bolontrade, Oscar Andriani, Carolina Bizama, Cristóbal Fresno, Osvaldo Podhajcer, Elmer Fernandez, Manuel Gidekel, Guillermo D Mazzolini, Mariana G García
New therapies are needed for advanced hepatocellular carcinoma (HCC) and the use of mesenchymal stromal cells (MSCs) carrying therapeutic genes is a promising strategy. HCC produce cytokines recruiting MSCs to the tumor milieu and modifying its biological properties. Our aim was to study changes generated on human MSCs exposed to conditioned media (CM) derived from human HCC fresh samples and xenografts. All CM shared similar cytokines expression pattern including CXCL1-2-3/GRO, CCL2/MCP-1 and CXCL8/IL-8 being the latter with the highest concentration...
October 6, 2017: Oncotarget
https://www.readbyqxmd.com/read/29113197/acidic-stress-induces-apoptosis-and-inhibits-angiogenesis-in-human-bone-marrow-derived-endothelial-progenitor-cells
#19
Shuai Huang, Peiheng He, Dongliang Xu, Jinglei Li, Xinsheng Peng, Yubo Tang
Bone marrow-derived endothelial progenitor cells (BM-EPCs) are exposed to acidotic environments in a variety of physiological and pathological conditions, including in tumors. However, the effect of acidosis on the function of BM-EPCs is still not fully understood. In the present study, BM-EPCs were isolated and cultured at an extracellular pH (pHe) of 6.5 or pHe 7.4 in vitro prior to various experiments being performed. Cellular proliferation, migration and tube formation ability were detected by DNA content quantification, Transwell assay and Matrigel-based angiogenesis assay...
November 2017: Oncology Letters
https://www.readbyqxmd.com/read/29105655/pre-metastatic-cancer-exosomes-induce-immune-surveillance-by-patrolling-monocytes-at-the-metastatic-niche
#20
Michael P Plebanek, Nicholas L Angeloni, Elena Vinokour, Jia Li, Anna Henkin, Dalia Martinez-Marin, Stephanie Filleur, Reshma Bhowmick, Jack Henkin, Stephen D Miller, Igal Ifergan, Yesung Lee, Iman Osman, C Shad Thaxton, Olga V Volpert
Metastatic cancers produce exosomes that condition pre-metastatic niches in remote microenvironments to favor metastasis. In contrast, here we show that exosomes from poorly metastatic melanoma cells can potently inhibit metastasis to the lung. These "non-metastatic" exosomes stimulate an innate immune response through the expansion of Ly6C(low) patrolling monocytes (PMo) in the bone marrow, which then cause cancer cell clearance at the pre-metastatic niche, via the recruitment of NK cells and TRAIL-dependent killing of melanoma cells by macrophages...
November 6, 2017: Nature Communications
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