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Adam R Wolfe, Nicholaus J Trenton, Bisrat G Debeb, Richard Larson, Brian Ruffell, Khoi Chu, Walter Hittelman, Michael Diehl, Jim M Reuben, Naoto T Ueno, Wendy A Woodward
Inflammatory breast cancer (IBC) is a unique and deadly disease with unknown drivers. We hypothesized the inflammatory environment contributes to the IBC phenotype. We used an in vitro co-culture system to investigate interactions between normal and polarized macrophages (RAW 264.7 cell line), bone-marrow derived mesenchymal stem cells (MSCs), and IBC cells (SUM 149 and MDA-IBC3). We used an in vivo model that reproduces the IBC phenotype by co-injecting IBC cells with MSCs into the mammary fat pad. Mice were then treated with a macrophage recruitment inhibitor, anti-CSF1...
October 15, 2016: Oncotarget
Patricia Pereiro, Gabriel Forn-Cuni, Antonio Figueras, Beatriz Novoa
Interferon-gamma has been typically described as a pro-inflammatory cytokine playing an important role in the resolution of both viral and bacterial diseases. Nevertheless, some anti-inflammatory functions are also attributed to this molecule. In this work we have characterized for the first time the turbot (Scophthalmus maximus) interferon-gamma gene (ifng) and its expression pattern under basal conditions, after type I IFNs administration, and viral and bacterial infection. The intramuscular injection of an expression plasmid encoding turbot Ifng (pMCV1...
October 11, 2016: Fish & Shellfish Immunology
G Galletti, F Caligaris-Cappio, M T S Bertilaccio
The development and progression of chronic B-cell tumors depend on a complex microenvironmental network of cells that include monocyte-derived macrophages. In chronic lymphocytic leukemia (CLL) the survival of malignant cells is supported in vitro by nurse-like cells, which differentiate from CD14(+) monocytes and have been identified as tumor-associated macrophages (TAMs). The role of the monocyte/macrophage lineage in CLL has been extensively studied in vitro, but only recently has been investigated in in vivo models...
October 14, 2016: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
Xiaoping Qing, Lindsay Rogers, Arthur Mortha, Yonit Lavin, Patricia Redecha, Priya D Issuree, Thorsten Maretzky, Miriam Merad, David McIlwain, Tak W Mak, Christopher M Overall, Carl P Blobel, Jane E Salmon
CSF1R (colony stimulating factor 1 receptor) is the main receptor for CSF1 and has crucial roles in regulating myelopoeisis. CSF1R can be proteolytically released from the cell surface by ADAM17 (A disintegrin and metalloprotease 17). Here, we identified CSF1R as a major substrate of ADAM17 in an unbiased degradomics screen. We explored the impact of CSF1R shedding by ADAM17 and its upstream regulator, inactive rhomboid protein 2 (iRhom2, gene name Rhbdf2), on homeostatic development of mouse myeloid cells...
September 7, 2016: European Journal of Immunology
Jingxian Ding, Chungen Guo, Pinghua Hu, Jun Chen, Qiuming Liu, Xiaobo Wu, Yali Cao, Jiong Wu
Despite the great progress in breast cancer research and treatment, measures for efficient targeting of triple‑negative breast cancer (TNBC) are still lacking. The well‑established dependency of cancer cells on their microenvironment suggests that targeting the tumor niche might form a novel therapeutic approach. We identified the tumor‑associated macrophage (TAM) infiltration in breast cancer tissues by immunohistochemistry, and analyzed overall survival (OS). U937 co‑cultures with MDA‑MB‑231, MDA‑MB‑468 and MCF‑7, respectively, to simulate in vivo cellular interactions were assessed...
September 6, 2016: International Journal of Oncology
Hui Zhao, Flora Kalish, Ronald J Wong, David K Stevenson
Infiltrating myeloid cells in pregnant uteri play critical roles in the establishment of the placenta and maintenance of normal pregnancies. Their recruitment and proliferation are primarily mediated by the interactions of cytokines and chemokines secreted locally with their corresponding receptors. Heme oxygenase-1 (HO-1) has various physiologic properties that contribute to placental vascular development, with deficiencies in HO-1 associated with pregnancy disorders. Here, we investigated the effect of HO-1 on myeloid cell infiltration into pregnant uteri using a partial HO-1-deficient (Het, HO-1(+/-)) mouse model...
July 28, 2016: Journal of Leukocyte Biology
Kristin A Sauter, Lindsey A Waddell, Zofia M Lisowski, Rachel Young, Lucas Lefevre, Gemma M Davis, Sara M Clohisey, Mary McCulloch, Elizabeth Magowan, Neil A Mabbott, Kim M Summers, David A Hume
Macrophage colony-stimulating factor (CSF1) is an essential growth and differentiation factor for cells of the macrophage lineage. To explore the role of CSF1 in steady-state control of monocyte production and differentiation and tissue repair, we previously developed a bioactive protein with a longer half-life in circulation by fusing pig CSF1 with the Fc region of pig IgG1a. CSF1-Fc administration to pigs expanded progenitor pools in the marrow and selectively increased monocyte numbers and their expression of the maturation marker CD163...
September 1, 2016: American Journal of Physiology. Gastrointestinal and Liver Physiology
Igor Theurl, Ingo Hilgendorf, Manfred Nairz, Piotr Tymoszuk, David Haschka, Malte Asshoff, Shun He, Louisa M S Gerhardt, Tobias A W Holderried, Markus Seifert, Sieghart Sopper, Ashley M Fenn, Atsushi Anzai, Sara Rattik, Cameron McAlpine, Milan Theurl, Peter Wieghofer, Yoshiko Iwamoto, Georg F Weber, Nina K Harder, Benjamin G Chousterman, Tara L Arvedson, Mary McKee, Fudi Wang, Oliver M D Lutz, Emanuele Rezoagli, Jodie L Babitt, Lorenzo Berra, Marco Prinz, Matthias Nahrendorf, Guenter Weiss, Ralph Weissleder, Herbert Y Lin, Filip K Swirski
Iron is an essential component of the erythrocyte protein hemoglobin and is crucial to oxygen transport in vertebrates. In the steady state, erythrocyte production is in equilibrium with erythrocyte removal. In various pathophysiological conditions, however, erythrocyte life span is compromised severely, which threatens the organism with anemia and iron toxicity. Here we identify an on-demand mechanism that clears erythrocytes and recycles iron. We show that monocytes that express high levels of lymphocyte antigen 6 complex, locus C1 (LY6C1, also known as Ly-6C) ingest stressed and senescent erythrocytes, accumulate in the liver via coordinated chemotactic cues, and differentiate into ferroportin 1 (FPN1, encoded by SLC40A1)-expressing macrophages that can deliver iron to hepatocytes...
August 2016: Nature Medicine
Anne-Laure Chéné, Sènan d'Almeida, Thibaut Blondy, Julie Tabiasco, Sophie Deshayes, Jean-François Fonteneau, Laurent Cellerin, Yves Delneste, Marc Grégoire, Christophe Blanquart
INTRODUCTION: Mesothelioma is a rare and aggressive cancer related to asbestos exposure. We recently showed that pleural effusions (PEs) from patients with mesothelioma contain high levels of the C-C motif chemokine ligand 2 (CCL2) inflammatory chemokine. In the present work, we studied the effect of CCL2 contained in mesothelioma samples, particularly on monocyte recruitment. Then, we studied the fate of these monocytes in malignant pleural mesothelioma (MPM) PEs and their impact on tumor cells' properties...
October 2016: Journal of Thoracic Oncology
Tatsuya Sasaki, Yuka Tanaka, Kasem Kulkeaw, Ayako Yumine-Takai, Keai Sinn Tan, Ryuichi Nishinakamura, Junji Ishida, Akiyoshi Fukamizu, Daisuke Sugiyama
The aorta-gonad-mesonephros (AGM) region contains intra-aortic clusters (IACs) thought to have acquired hematopoietic stem cell (HSC) potential in vertebrate embryos. To assess extrinsic regulation of IACs in the AGM region, we employed mouse embryos harboring a Sall1-GFP reporter gene, which allows identification of mesonephros cells based on GFP expression. Analysis of AGM region tissue sections confirmed mesonephros GFP expression. Mesonephric cells sorted at E10.5 expressed mRNA encoding Csf1, a hematopoietic cytokine, and corresponding protein, based on real-time PCR and immunocytochemistry, respectively...
June 20, 2016: Stem Cell Reviews
Eric L Staals, Stefano Ferrari, Davide M Donati, Emanuela Palmerini
At present, the optimal treatment strategy in patients with diffuse-type tenosynovial giant cell tumour (D-TGCT) is unclear. The purpose of this review was to describe current treatment options, and to highlight recent developments in the knowledge of the molecular pathogenesis of D-TGCT as well as related therapeutic implications. Epidemiology, clinical features, and the pathogenesis of D-TGCT and the most widely used treatment modalities are described. D-TGCT is a benign clonal neoplastic proliferation arising from the synovium...
August 2016: European Journal of Cancer
Masaru Katoh
Fibroblast growth factor (FGF)2, FGF4, FGF7 and FGF20 are representative paracrine FGFs binding to heparan-sulfate proteoglycan and fibroblast growth factor receptors (FGFRs), whereas FGF19, FGF21 and FGF23 are endocrine FGFs binding to Klotho and FGFRs. FGFR1 is relatively frequently amplified and overexpressed in breast and lung cancer, and FGFR2 in gastric cancer. BCR-FGFR1, CNTRL-FGFR1, CUX1-FGFR1, FGFR1OP-FGFR1, MYO18A-FGFR1 and ZMYM2-FGFR1 fusions in myeloproliferative neoplasms are non-receptor-type FGFR kinases, whereas FGFR1-TACC1, FGFR2-AFF3, FGFR2-BICC1, FGFR2-PPHLN1, FGFR3-BAIAP2L1 and FGFR3-TACC3 fusions in solid tumors are transmembrane-type FGFRs with C-terminal alterations...
July 2016: International Journal of Molecular Medicine
Hiroaki Suzuki, Tadakazu Hisamatsu, Sayako Chiba, Kiyoto Mori, Mina T Kitazume, Katsuyoshi Shimamura, Nobuhiro Nakamoto, Katsuyoshi Matsuoka, Hirotoshi Ebinuma, Makoto Naganuma, Takanori Kanai
Cellular metabolic state and individual metabolites have been reported to regulate the functional phenotype of immune cells. Cytokine production by regulatory and inflammatory macrophages is thought to mainly involve fatty acid oxidation and glycolysis, respectively, which fuel mitochondrial oxidative phosphorylation. However, the association between metabolic pathways and the acquisition of specific macrophage phenotypes remains unclear. This study assessed the relationship between glycolysis and the differentiation of regulatory macrophages...
August 2016: Immunology Letters
Stephen Iwanowycz, Junfeng Wang, Johnie Hodge, Yuzhen Wang, Fang Yu, Daping Fan
Macrophage infiltration correlates with severity in many types of cancer. Tumor cells recruit macrophages and educate them to adopt an M2-like phenotype through the secretion of chemokines and growth factors, such as MCP1 and CSF1. Macrophages in turn promote tumor growth through supporting angiogenesis, suppressing antitumor immunity, modulating extracellular matrix remodeling, and promoting tumor cell migration. Thus, tumor cells and macrophages interact to create a feedforward loop supporting tumor growth and metastasis...
August 2016: Molecular Cancer Therapeutics
Anna Martínez-Muriana, Renzo Mancuso, Isaac Francos-Quijorna, Adrian Olmos-Alonso, Rosario Osta, V Hugh Perry, Xavier Navarro, Diego Gomez-Nicola, Ruben López-Vales
Inflammation is a common neuropathological feature in several neurological disorders, including amyotrophic lateral sclerosis (ALS). We have studied the contribution of CSF1R signalling to inflammation in ALS, as a pathway previously reported to control the expansion and activation of microglial cells. We found that microglial cell proliferation in the spinal cord of SOD1(G93A) transgenic mice correlates with the expression of CSF1R and its ligand CSF1. Administration of GW2580, a selective CSF1R inhibitor, reduced microglial cell proliferation in SOD1(G93A) mice, indicating the importance of CSF1-CSF1R signalling in microgliosis in ALS...
2016: Scientific Reports
Nunzia Pastore, Owen A Brady, Heba I Diab, José A Martina, Lu Sun, Tuong Huynh, Jeong-A Lim, Hossein Zare, Nina Raben, Andrea Ballabio, Rosa Puertollano
The activation of transcription factors is critical to ensure an effective defense against pathogens. In this study we identify a critical and complementary role of the transcription factors TFEB and TFE3 in innate immune response. By using a combination of chromatin immunoprecipitation, CRISPR-Cas9-mediated genome-editing technology, and in vivo models, we determined that TFEB and TFE3 collaborate with each other in activated macrophages and microglia to promote efficient autophagy induction, increased lysosomal biogenesis, and transcriptional upregulation of numerous proinflammatory cytokines...
August 2, 2016: Autophagy
Huayang Wang, Qianqian Shao, Jintang Sun, Chao Ma, Wenjuan Gao, Qingjie Wang, Lei Zhao, Xun Qu
Tumor-infiltrated macrophages were potential targets of the immune therapy for patients with colon cancer. Colony stimulating factor 1 (CSF1) is a primary chemoattractant and functional regulator for macrophages, and therefore would be a feasible intervention for the macrophage-targeting therapeutics. However, the expression of CSF1 in colon cancer microenvironment and its roles in cancer development is largely unknown. In the present study, we found that CSF1 was over-expressed exclusively in colon cancer cells and was correlated with macrophages infiltration...
April 2016: Oncoimmunology
Shin Foong Ngiow, Katrina M Meeth, Kimberley Stannard, Deborah S Barkauskas, Gideon Bollag, Marcus Bosenberg, Mark J Smyth
The presence of colony stimulating factor-1 (CSF1)/CSF1 receptor (CSF1R)-driven tumor-infiltrating macrophages and myeloid-derived suppressor cells (MDSCs) is shown to promote targeted therapy resistance. In this study, we demonstrate the superior effect of a combination of CSF1R inhibitor, PLX3397 and BRAF inhibitor, PLX4720, in suppressing primary and metastatic mouse BRAF(V600E) melanoma. Using flow cytometry to assess SM1WT1 melanoma-infiltrating leukocytes immediately post therapy, we found that PLX3397 reduced the recruitment of CD11b(+) Gr1(lo) and CD11b(+) Gr1(int) M2-like macrophages, but this was accompanied by an accumulation of CD11b(+) Gr1(hi) cells...
March 2016: Oncoimmunology
Wei Dang, Zailong Qin, Songqing Fan, Qiuyuan Wen, Yuanjun Lu, Jia Wang, Xuemei Zhang, Lingyu Wei, Wei He, Qiurong Ye, Qun Yan, Guiyuan Li, Jian Ma
We previously reported that miR-1207-5p can inhibit epithelial-mesenchymal transition (EMT) induced by growth factors such as EGF and TGF-β, but the exact mechanism is unclear. Here we identified that Colony stimulating factor 1 (CSF1) is a target gene of miR-1207-5p. CSF1 controls the production, differentiation and function of macrophage and promotes the release of proinflammatory chemokines. We showed that miR-1207-5p inhibited lung cancer cell A549 proliferation, migration and invasion in vitro, and suppressed the STAT3 and AKT signalings...
May 31, 2016: Oncotarget
Qiuming Chen, Yanjun Wu, Mingyuan Zhang, Wenwen Xu, Xiaoping Guo, Xueyu Yan, Haiying Deng, Qinyang Jiang, Xiurong Yang, Ganqiu Lan, Yafen Guo, Guangsheng Qin, Hesheng Jiang
Owing to the difficulty in obtaining mammary gland tissue from lactating animals, it is difficult to test the expression levels of genes in mammary gland. The aim of the current study was to identify if milk fat globule (MFG) in buffalo milk was an alternative to mammary gland (MG) and milk somatic cell (MSC) for gene expression analysis. Six buffalos in late lactation were selected to collect MFG and MSC, and then MG was obtained by surgery. MFG was stained with acridine orange to successfully visualise RNA and several cytoplasmic crescents in MFG...
May 2016: Journal of Dairy Research
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