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Bone marrow microenvironment

Yawara Kawano, Oksana Zavidij, Jihye Park, Michele Moschetta, Katsutoshi Kokubun, Tarek H Mouhieddine, Salomon Manier, Yuji Mishima, Naoka Murakami, Mark Bustoros, Romanos Sklavenitis Pistofidis, Mairead Reidy, Yu J Shen, Mahshid Rahmat, Pavlo Lukyanchykov, Esilida Sula Karreci, Shokichi Tsukamoto, Jiantao Shi, Satoshi Takagi, Daisy Huynh, Antonio Sacco, Yu-Tzu Tai, Marta Chesi, P Leif Bergsagel, Aldo M Roccaro, Jamil Azzi, Irene M Ghobrial
Despite significant advances in the treatment of multiple myeloma (MM), most patients succumb to disease progression. One of the major immunosuppressive mechanisms that is believed to play a role in myeloma progression, is the expansion of regulatory T-cells (Tregs). In this study, we demonstrate that myeloma cells drive Treg expansion and activation by secreting type-1 interferon (IFN). Blocking IFNAR1 (interferon alpha and beta receptor 1) on Tregs significantly decreases both, myeloma-associated Treg immunosuppressive function and myeloma progression...
March 20, 2018: Journal of Clinical Investigation
Mariusz Z Ratajczak, Mateusz Adamiak, Monika Plonka, Ahmed Abdel-Latif, Janina Ratajczak
Hematopoietic stem/progenitor cells (HSPCs) circulate in peripheral blood (PB) under normal conditions and their number increases in response to stress, inflammation, tissue/organ injury, and may increase up to 100-fold after administration of mobilization-inducing drugs. Mounting evidence suggests that mobilizing agent-induced mobilization of HSPCs from bone marrow into PB is a result of innate immunity-mediated sterile inflammation in the bone marrow (BM) microenvironment. A critical initiating role in this process is played by tissue/organ injury-mediated or pharmacologically induced release from bone marrow-residing granulocytes and monocytes of (i) danger-associated molecular patterns (DAMPs), (ii) reactive oxygen species (ROS), and (iii) proteolytic and lipolytic enzymes...
March 5, 2018: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
Joshua T Eggold, Erinn B Rankin
The regulation of erythropoiesis in the bone marrow microenvironment is a carefully orchestrated process that is dependent upon both systemic and local cues. Systemic erythropoietin (EPO) production by renal interstitial cells plays a critical role in maintaining erythropoietic homeostasis. In addition, there is increasing clinical and preclinical data linking changes in EPO and erythropoiesis to altered skeletal homeostasis, suggesting a functional relationship between the regulation of erythropoiesis and bone homeostasis...
March 15, 2018: Bone
Kyohei Nakamura, Sahar Kassem, Alice Cleynen, Marie-Lorraine Chrétien, Camille Guillerey, Eva Maria Putz, Tobias Bald, Irmgard Förster, Slavica Vuckovic, Geoffrey R Hill, Seth L Masters, Marta Chesi, P Leif Bergsagel, Hervé Avet-Loiseau, Ludovic Martinet, Mark J Smyth
Tumor-promoting inflammation and avoiding immune destruction are hallmarks of cancer. Here, we demonstrate that the pro-inflammatory cytokine interleukin (IL)-18 is critically involved in these hallmarks in multiple myeloma (MM). Mice deficient for IL-18 were remarkably protected from Vk∗ MYC MM progression in a CD8+ T cell-dependent manner. The MM-niche-derived IL-18 drove generation of myeloid-derived suppressor cells (MDSCs), leading to accelerated disease progression. A global transcriptome analysis of the immune microenvironment in 73 MM patients strongly supported the negative impact of IL-18-driven MDSCs on T cell responses...
March 1, 2018: Cancer Cell
Jillian Cornish, Tao Wang, Jian-Ming Lin
PURPOSE OF REVIEW: The goal of this review is to gain a better understanding of marrow adipocyte development, its regulation of energy, and its characterization responsible for bone homeostasis. RECENT FINDINGS: Despite major advances in uncovering the complex association of bone-fat in the marrow, the underlying basic biological process of adipose tissue development, as well as its interaction with bone homeostasis in pathophysiological conditions, is still not well understood...
March 16, 2018: Current Osteoporosis Reports
Karin Kohlstedt, Caroline Trouvain, Timo Frömel, Thomas Mudersbach, Reinhard Henschler, Ingrid Fleming
In addition to being a peptidase, the angiotensin-converting enzyme (ACE) can be phosphorylated and involved in signal transduction. We evaluated the role of ACE in granulocyte-colony-stimulating factor (G-CSF)-induced hematopoietic progenitor cell (HPC) mobilization and detected a significant increase in mice-lacking ACE. Transplantation experiments revealed that the loss of ACE in the HPC microenvironment rather than in the HPCs increased mobilization. Indeed, although ACE was expressed by a small population of bone-marrow cells, it was more strongly expressed by endosteal bone...
March 17, 2018: Basic Research in Cardiology
Emma V Morris, Claire M Edwards
Multiple Myeloma (MM) is an incurable haematological malignancy and is the second most common blood cancer in adults; it is caused by the clonal expansion of abnormal plasma cells within the bone marrow characterized by osteolytic bone lesions, bone pain, renal disease, and immunodeficiency. MM cells infiltrate the bone marrow where they hijack the microenvironment to sustain growth and survival. The contribution to this process by resident bone cells is well defined. However, the role of bone marrow adipocytes is less clear...
March 13, 2018: Bone
Steven M Kornblau, Peter P Ruvolo, Rui-Yu Wang, V Lokesh Battula, Elisabeth J Shpall, Vivian R Ruvolo, Teresa McQueen, YiHua Qui, Zhihong Zeng, Sherry Pierce, Rodrigo Jacamo, Suk-Young Yoo, Phuong M Le, Jeffery Sun, Numsen Hail, Marina Konopleva, Michael Andreeff
Mesenchymal stromal cells support acute myeloid leukemia cell survival in the bone marrow microenvironment. Protein expression profiles of acute myeloid leukemia-derived mesenchymal stromal cells are unknown. Reverse phase protein array analysis was performed to compare expression of 151 proteins from acute myeloid leukemia mesenchymal stromal cells (n = 106) with mesenchymal stromal cells from healthy donors (n = 71). Protein expression differed significantly between the two groups with nineteen proteins overexpressed in leukemia stromal cells and nine overexpressed in normal stromal cells...
March 15, 2018: Haematologica
Song Xu, Kim De Veirman, Ann De Becker, Karin Vanderkerken, Ivan Van Riet
Multiple myeloma (MM) is a malignant plasma cell (PC) disorder, characterized by a complex interactive network of tumour cells and the bone marrow (BM) stromal microenvironment, contributing to MM cell survival, proliferation and chemoresistance. Mesenchymal stem cells (MSCs) represent the predominant stem cell population of the bone marrow stroma, capable of differentiating into multiple cell lineages, including fibroblasts, adipocytes, chondrocytes and osteoblasts. MSCs can migrate towards primary tumours and metastatic sites, implying that these cells might modulate tumour growth and metastasis...
February 22, 2018: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
Antonella Cotoia, Lucia Mirabella, Sabrina Altamura, Rachele Villani, Flavia Marchese, Giuseppe Ferrara, Karim Mariano, Tullo Livio, Gilda Cinnella
BACKGROUND: Sepsis caused by complicated intra-abdominal infection is associated with high mortality. Loss of endothelial barrier integrity, inflammation, and impaired cellular oxygen have been shown to be primary contributors to sepsis. To date, little is known regarding the pathway for the mobilization of endothelial progenitor cells (EPCs) from the bone marrow in sepsis whereas stromal-cell-derived factor 1a (SDF-1a) and hypoxia inducible factor 1 (HIF-1) seem to have a role in the EPC response to hypoxic microenvironments...
March 12, 2018: Trials
Shayna E Thomas-Jardin, Mohammed S Kanchwala, Joan Jacob, Sana Merchant, Rachel K Meade, Nagham M Gahnim, Afshan F Nawas, Chao Xing, Nikki A Delk
BACKGROUND: In immunosurveillance, bone-derived immune cells infiltrate the tumor and secrete inflammatory cytokines to destroy cancer cells. However, cancer cells have evolved mechanisms to usurp inflammatory cytokines to promote tumor progression. In particular, the inflammatory cytokine, interleukin-1 (IL-1), is elevated in prostate cancer (PCa) patient tissue and serum, and promotes PCa bone metastasis. IL-1 also represses androgen receptor (AR) accumulation and activity in PCa cells, yet the cells remain viable and tumorigenic; suggesting that IL-1 may also contribute to AR-targeted therapy resistance...
March 11, 2018: Prostate
Emilie Coppin, Jonathan Florentin, Sathish Babu Vasamsetti, Anagha Arunkumar, John Sembrat, Mauricio Rojas, Dutta Partha
Splenic hematopoiesis is crucial to the pathogenesis of diseases including myocardial infarction and atherosclerosis. The spleen acts as a reservoir of myeloid cells, which are quickly expelled out in response to acute inflammation. In contrast to the well-defined bone marrow hematopoiesis, the cellular and molecular components sustaining splenic hematopoiesis are poorly understood. Surprisingly, we found that, unlike quiescent bone marrow hematopoietic stem cells (HSC), most of splenic HSC are in the G1 phase in C57BL/6 mice...
March 11, 2018: Immunology and Cell Biology
Pei Zhang, Xuguang Hu, Bin Liu, Zhe Liu, Cong Liu, Jianming Cai, Fu Gao, Jianguo Cui, Bailong Li, Yanyong Yang
BACKGROUND Carbon ion radiotherapy has been shown to be more effective in cancer radiotherapy than photon irradiation. Influence of carbon ion radiation on cancer microenvironment is very important for the outcomes of radiotherapy. Tumor-infiltrating dendritic cells (DCs) play critical roles in cancer antigen processing and antitumor immunity. However, there is scant literature covering the effects of carbon ion radiation on DCs. In this study, we aimed to uncover the impact of carbon ion irradiation on bone marrow derived DCs...
March 11, 2018: Medical Science Monitor: International Medical Journal of Experimental and Clinical Research
Wadie D Mahauad-Fernandez, Chioma M Okeoma
Bone marrow stromal antigen 2 (BST-2) also known as Tetherin has been implicated in the growth and progression of many cancers. BST-2 employs its pro-tumor effects through the formation of BST-2:BST-2 dimers which ultimately promotes cell to cell and cell to matrix adhesion, cell motility, survival, and growth. The aim of this study was to evaluate the effect of a novel BST-2-based peptide-B49 on adhesion and growth of breast cancer cells. Homotypic/heterotypic adhesion, three-dimensional spheroid formation, and anchorage-independent growth were used to assess the effect of B49 on cell adhesion and growth...
March 9, 2018: Scientific Reports
Agnieszka Barchnicka, Małgorzata Olejniczak-Nowakowska, Karolina Krupa-Kotara, Sebastian Grosicki
Angiogenesis plays a significant role in oncogenesis, and thus it has become an attractive target for cancer treatment. It is the formation of new blood vessels that occurs physiologically as well as under pathological conditions, and may influence cancer proliferation and survival. The current therapeutic approach in oncology includes conventional chemotherapy in combination with biologically-based treatment in various perspectives, targeting not only the malignant cells, but also its microenvironment. Target treatment might be less toxic than conventional chemotherapy...
February 2018: Advances in Clinical and Experimental Medicine: Official Organ Wroclaw Medical University
Leland Metheny, Saada Eid, Karen Lingas, Racheli Ofir, Lena Pinzur, Howard Meyerson, Hillard M Lazarus, Alex Y Huang
Late-term complications of hematopoietic cell transplantation (HCT) are numerous and include incomplete engraftment. One possible mechanism of incomplete engraftment after HCT is cytokine-mediated suppression or dysfunction of the bone marrow microenvironment. Mesenchymal stromal cells (MSCs) elaborate cytokines that nurture or stimulate the marrow microenvironment by several mechanisms. We hypothesize that the administration of exogenous MSCs may modulate the bone marrow milieu and improve peripheral blood count recovery in the setting of incomplete engraftment...
2018: Frontiers in Medicine
Mallika Ghosh, Shobha Thangada, Oisharya Dasgupta, Kamal M Khanna, Harold T Yamase, Michael Kashgarian, Timothy Hla, Linda H Shapiro, Fernando A Ferrer
Sphingosine Kinase-2 (Sphk2) is responsible for the production of the bioactive lipid Sphingosine-1 Phosphate, a key regulator of tissue repair. Here we address the in vivo significance of Sphingosine Kinase -2 in renal inflammation/fibrosis in response to unilateral ureteral obstruction using both genetic and pharmacological strategies. Obstructed kidneys of Sphk2-/- mice showed reduced renal damage and diminished levels of the renal injury markers TGFβ1 and αSMA when compared to wild type controls. We found a consistently significant increase in anti-inflammatory (M2) macrophages in obstructed Sphk2-/- kidneys by flow cytometry and a decrease in mRNA levels of the inflammatory cytokines, MCP1, TNFα, CXCL1 and ILβ1, suggesting an anti-inflammatory bias in the absence of Sphk2...
2018: PloS One
Laura Pietrovito, Angela Leo, Valentina Gori, Matteo Lulli, Matteo Parri, Valentina Becherucci, Luisa Piccini, Franco Bambi, Maria Letizia Taddei, Paola Chiarugi
There is growing evidence to suggest that bone marrow-derived mesenchymal stem cells (BM-MSCs) are key players in tumor stroma. Here, we investigated the cross-talk between BM-MSCs and osteosarcoma (OS) cells. We revealed a strong tropism of BM-MSCs towards these tumor cells, and identified MCP-1, GRO-α and TGF-β1 as pivotal factors for BM-MSC chemotaxis. Once in contact with OS cells, BM-MSCs transdifferentiate into cancer-associated fibroblasts, further increasing MCP-1, GRO-α, IL-6 and IL-8 levels in the tumor microenvironment...
March 8, 2018: Molecular Oncology
Leila Farahmand, Rezvan Esmaeili, Leila Eini, Keivan Majidzadeh-A
Purpose: Bone marrow-derived mesenchymal stem cells (MSCs) have the potential ability to differentiate into bone, muscle, fat, and cartilage lineage cells. Furthermore, MSCs are known to migrate into tumor-associated stroma of cancer. This tumor microenvironment consists of a dynamic network of growth factors, immune cells, fibroblasts, extracellular matrix, and MSCs. MSCs as nonhematopoietic stem cells affect tumor, epithelial cells by alteration proliferative capacity, morphology, and aggregation pattern of tumor cells...
January 2018: Journal of Cancer Research and Therapeutics
Pingnan Xiao, Monika Dolinska, Lakshmi Sandhow, Makoto Kondo, Anne-Sofie Johansson, Thibault Bouderlique, Ying Zhao, Xidan Li, Marios Dimitriou, George Z Rassidakis, Eva Hellström-Lindberg, Nagahiro Minato, Julian Walfridsson, David T Scadden, Mikael Sigvardsson, Hong Qian
Mutations of signal-induced proliferation-associated gene 1 ( SIPA1 ), a RAP1 GTPase-activating protein, were reported in patients with juvenile myelomonocytic leukemia, a childhood myelodysplastic/myeloproliferative neoplasm (MDS/MPN). Sipa1 deficiency in mice leads to the development of age-dependent MPN. However, Sipa1 expression in bone marrow (BM) microenvironment and its effect on the pathogenesis of MPN remain unclear. We here report that Sipa1 is expressed in human and mouse BM stromal cells and downregulated in these cells from patients with MPN or MDS/MPN at diagnosis...
March 13, 2018: Blood Advances
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