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CCL2 AND CANCER

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https://www.readbyqxmd.com/read/28514653/the-presence-of-interleukin-13-at-pancreatic-adm-panin-lesions-alters-macrophage-populations-and-mediates-pancreatic-tumorigenesis
#1
Geou-Yarh Liou, Ligia Bastea, Alicia Fleming, Heike Döppler, Brandy H Edenfield, David W Dawson, Lizhi Zhang, Nabeel Bardeesy, Peter Storz
The contributions of the innate immune system to the development of pancreatic cancer are still ill defined. Inflammatory macrophages can initiate metaplasia of pancreatic acinar cells to a duct-like phenotype (acinar-to-ductal metaplasia [ADM]), which then gives rise to pancreatic intraepithelial neoplasia (PanIN) when oncogenic KRas is present. However, it remains unclear when and how this inflammatory macrophage population is replaced by tumor-promoting macrophages. Here, we demonstrate the presence of interleukin-13 (IL-13), which can convert inflammatory into Ym1+ alternatively activated macrophages, at ADM/PanIN lesions...
May 16, 2017: Cell Reports
https://www.readbyqxmd.com/read/28508873/mutant-kras-promotes-malignant-pleural-effusion-formation
#2
Theodora Αgalioti, Anastasios D Giannou, Anthi C Krontira, Nikolaos I Kanellakis, Danai Kati, Malamati Vreka, Mario Pepe, Μagda Spella, Ioannis Lilis, Dimitra E Zazara, Eirini Nikolouli, Nikolitsa Spiropoulou, Andreas Papadakis, Konstantina Papadia, Apostolos Voulgaridis, Vaggelis Harokopos, Panagiota Stamou, Silke Meiners, Oliver Eickelberg, Linda A Snyder, Sophia G Antimisiaris, Dimitrios Kardamakis, Ioannis Psallidas, Antonia Μarazioti, Georgios T Stathopoulos
Malignant pleural effusion (MPE) is the lethal consequence of various human cancers metastatic to the pleural cavity. However, the mechanisms responsible for the development of MPE are still obscure. Here we show that mutant KRAS is important for MPE induction in mice. Pleural disseminated, mutant KRAS bearing tumour cells upregulate and systemically release chemokine ligand 2 (CCL2) into the bloodstream to mobilize myeloid cells from the host bone marrow to the pleural space via the spleen. These cells promote MPE formation, as indicated by splenectomy and splenocyte restoration experiments...
May 16, 2017: Nature Communications
https://www.readbyqxmd.com/read/28507122/control-of-metastatic-niche-formation-by-targeting-apba3-mint3-in-inflammatory-monocytes
#3
Toshiro Hara, Hiroki J Nakaoka, Tetsuro Hayashi, Kouhei Mimura, Daisuke Hoshino, Masahiro Inoue, Fumitaka Nagamura, Yoshinori Murakami, Motoharu Seiki, Takeharu Sakamoto
Cancer metastasis is intricately orchestrated by both cancer and normal cells, such as endothelial cells and macrophages. Monocytes/macrophages, which are often co-opted by cancer cells and promote tumor malignancy, acquire more than half of their energy from glycolysis even during normoxic conditions. This glycolytic activity is maintained during normoxia by the functions of hypoxia inducible factor 1 (HIF-1) and its activator APBA3. The mechanism by which APBA3 inhibition partially suppresses macrophage function and affects cancer metastasis is of interest in view of avoidance of the adverse effects of complete suppression of macrophage function during therapy...
May 15, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28498437/autocrine-expression-of-the-epidermal-growth-factor-receptor-ligand-heparin-binding-egf-like-growth-factor-in-cervical-cancer
#4
Marlies Schrevel, E Michelle Osse, Frans A Prins, J Baptist M Z Trimbos, Gert Jan Fleuren, Arko Gorter, Ekaterina S Jordanova
In cervical cancer, the epidermal growth factor receptor (EGFR) is overexpressed in 70-90% of the cases and has been associated with poor prognosis. EGFR-based therapy is currently being explored in cervical cancer. We investigated which EGFR ligand is primarily expressed in cervical cancer and which cell type functions as the major source of this ligand. We hypothesized that macrophages are the main source of EGFR ligands and that a paracrine loop between tumor cells and macrophages is responsible for ligand expression...
May 3, 2017: International Journal of Oncology
https://www.readbyqxmd.com/read/28475599/susd2-promotes-tumor-associated-macrophage-recruitment-by-increasing-levels-of-mcp-1-in-breast-cancer
#5
Elizabeth M Hultgren, Mitch E Patrick, Rick L Evans, Catherine T Stoos, Kristi A Egland
Tumor-associated macrophages (TAMs) play a role in tumor angiogenesis and are recruited into the tumor microenvironment (TME) by secreted chemokines, including Monocyte Chemoattractant Protein-1 (MCP-1/CCL2). Angiogenesis is required to sustain proliferation and enable metastasis of breast cancer (BCa) cells. Understanding the underlying mechanisms of TAM recruitment would allow for the identification of desperately needed novel drug targets. Sushi Domain Containing 2 (SUSD2), a transmembrane protein on BCa cells, was previously shown to promote tumor angiogenesis in a murine model...
2017: PloS One
https://www.readbyqxmd.com/read/28441391/apigenin-inhibits-tnf%C3%AE-il-1%C3%AE-induced-ccl2-release-through-ikbk-epsilon-signaling-in-mda-mb-231-human-breast-cancer-cells
#6
David Bauer, Natalie Redmon, Elizabeth Mazzio, Karam F Soliman
Mortality associated with breast cancer is attributable to aggressive metastasis, to which TNFα plays a central orchestrating role. TNFα acts on breast tumor TNF receptors evoking the release of chemotactic proteins (e.g. MCP-1/CCL2). These proteins direct inward infiltration/migration of tumor-associated macrophages (TAMs), tumor-associated neutrophils (TANs), myeloid-derived suppressor cells (MDSCs), T-regulatory cells (Tregs), T helper IL-17-producing cells (Th17s), metastasis-associated macrophages (MAMs) and cancer-associated fibroblasts (CAFs)...
2017: PloS One
https://www.readbyqxmd.com/read/28424660/ccl2-monocyte-chemoattractant-protein-1-and-parathyroid-hormone-action-on-bone
#7
REVIEW
Jawed Akhtar Siddiqui, Nicola C Partridge
Chemokines are small molecules that play a crucial role as chemoattractants for several cell types, and their components are associated with host immune responses and repair mechanisms. Chemokines selectively recruit monocytes, neutrophils, and lymphocytes and induce chemotaxis through the activation of G protein-coupled receptors. Two well-described chemokine families (CXC and CC) are known to regulate the localization and trafficking of immune cells in cases of injury, infection, and tumors. Monocyte chemoattractant protein 1 (MCP-1/CCL2) is one of the important chemokines from the CC family that controls migration and infiltration of monocytes/macrophages during inflammation...
2017: Frontiers in Endocrinology
https://www.readbyqxmd.com/read/28424406/targeting-ccr2-with-its-antagonist-suppresses-viability-motility-and-invasion-by-downregulating-mmp-9-expression-in-non-small-cell-lung-cancer-cells
#8
Jun An, Ying Xue, Meijun Long, Ge Zhang, Junhang Zhang, Hang Su
Non-small cell lung cancer (NSCLC) is the most common type of lung cancer, which is the leading cancer killer in the world. Despite the recent advances in its diagnosis and therapy, the prognosis of NSCLC patients remains very poor, mainly due to the development of drug resistance and metastasis. Both the chemokine network and the matrix metalloproteinase (MMP) system play important roles in cancer cell metastasis. The disruption of CCL2/CCR2 chemokine signaling has been shown to suppress cancer cellviability and metastasis...
April 5, 2017: Oncotarget
https://www.readbyqxmd.com/read/28405506/oral-delivery-of-tumor-microparticle-vaccines-activates-nod2-signaling-pathway-in-ileac-epithelium-rendering-potent-antitumor-t-cell-immunity
#9
Wenqian Dong, Huafeng Zhang, Xiaonan Yin, Yuying Liu, Degao Chen, Xiaoyu Liang, Xun Jin, Jiadi Lv, Jingwei Ma, Ke Tang, Zhuowei Hu, Xiaofeng Qin, Bo Huang
Exploiting gut mucosal immunity to design new antitumor vaccination strategy remains unexplored. Tumor cell-derived microparticles (T-MP) are natural biomaterials that are capable of delivering tumor antigens and innate signals to dendritic cells (DC) for tumor-specific T cell immunity. Here, we show that T-MPs by oral vaccination route effectively access and activate mucosal epithelium, leading to subsequent antitumor T cell responses. Oral vaccination of T-MPs generated potent inhibitory effect against the growth of B16 melanoma and CT26 colon cancer in mice, which required both T cell and DC activation...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/28347237/specific-tumor-derived-ccl2-mediated-by-pyruvate-kinase-m2-in-colorectal-cancer-cells-contributes-to-macrophage-recruitment-in-tumor-microenvironment
#10
Kejian Zou, Yaodong Wang, Yan Hu, Liansheng Zheng, Wanfu Xu, Guoxin Li
Development of colorectal cancer has been considered as a result of imbalance of pro- and anti-inflammatory intestinal microenvironment accompanied by macrophage recruitment. Despite macrophages are implicated in remodeling tumor microenvironment, the mechanism of macrophage recruitment is not fully elucidated yet. In this study, we reported clinical association of highly expressed pyruvate kinase M2 in colorectal cancer with macrophage attraction. The conditioned medium from Caco-2 and HT-29 cells with depleted pyruvate kinase M2 dramatically reduced macrophage recruitment, which is reversed by addition of, a critical chemotaxis factor to macrophage migration, rCCL2...
March 2017: Tumour Biology: the Journal of the International Society for Oncodevelopmental Biology and Medicine
https://www.readbyqxmd.com/read/28344868/langerhans-cells-and-nk-cells-cooperate-in-the-inhibition-of-chemical-skin-carcinogenesis
#11
Daniela Ortner, Christoph H Tripp, Kerstin Komenda, Sandrine Dubrac, Bernhard Zelger, Martin Hermann, Wolfgang Doppler, Piotr Z Tymoszuk, Louis Boon, Björn E Clausen, Patrizia Stoitzner
Tissue immunosurveillance is an important mechanism to prevent cancer. Skin treatment with the carcinogen 7,12-dimethylbenz(a)anthracene (DMBA), followed by the tumor promoter 12-O-tetra-decanoyl-phorbol-13-acetate (TPA), is an established murine model for squamous cell carcinoma (SCC). However, the innate immunological events occurring during the initiation of chemical carcinogenesis with DMBA remain elusive. Here, we discovered that natural killer (NK) cells and Langerhans cells (LC) cooperate to impair this oncogenic process in murine skin...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/28339085/integrated-analysis-of-mrna-and-mirna-expression-profiles-in-pancreatic-ductal-adenocarcinoma
#12
Hongwei Sun, Liang Zhao, Kehua Pan, Zhao Zhang, Mengtao Zhou, Guoquan Cao
In the present study, to investigate the potential molecular mechanism of pancreatic ductal adenocarcinoma (PDAC), mRNA and miRNA expression profiles were integrated for systematic analysis. Results showed that a total of 76 common differentially expressed genes (DEGs) were identified from 2 mRNA expression profiles that contained 39 tumor and 15 normal samples. Notably, the tumor and normal samples were able to be clearly classified into 4 groups based on the DEGs. mRNA‑miRNA regulation network analysis indicated that 22 out of the 76 DEGs including MUC4, RRM2 and CCL2 are regulated by 5 reported miRNAs...
March 24, 2017: Oncology Reports
https://www.readbyqxmd.com/read/28337194/il-1%C3%AE-il-8-and-matrix-metalloproteinases-1-2-and-10-are-enriched-upon-monocyte-breast-cancer-cell-cocultivation-in-a-matrigel-based-three-dimensional-system
#13
Nancy Adriana Espinoza-Sánchez, Gloria Karina Chimal-Ramírez, Alejandra Mantilla, Ezequiel Moisés Fuentes-Pananá
Breast cancer remains the first cancer-related cause of death in women worldwide, particularly in developing countries in which most cases are diagnosed in late stages. Although most cancer studies are based in the genetic or epigenetic changes of the tumor cells, immune cells within the tumor stroma often cooperate with cancer progression. Particularly, monocytes are attracted to the tumor primary site in which they are differentiated into tumor-associated macrophages that facilitate tumor cell invasion and metastasis...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28302482/fap-positive-fibroblasts-induce-immune-checkpoint-blockade-resistance-in-colorectal-cancer-via-promoting-immunosuppression
#14
Lingling Chen, Xiangting Qiu, Xinhua Wang, Jian He
Immune checkpoint blockades that significantly prolonged survival of melanoma patients have been less effective on colorectal cancer (CRC) patients. Growing evidence suggested that fibroblast activation protein-alpha (FAP) on cancer associate fibroblasts (CAFs) has critical roles in regulating antitumor immune response by inducing tumor-promoting inflammation. In this study, we explored the roles of FAP in regulating the tumor immunity and immune checkpoint blockades resistance in CRC experimental systems. We found that CAFs with high FAP expression could induce immune checkpoint blockade resistance in CRC mouse model...
May 20, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28267621/targeting-hepatic-macrophages-to-treat-liver-diseases
#15
REVIEW
Frank Tacke
Our view on liver macrophages in the context of health and disease has been reformed by the recognition of a remarkable heterogeneity of phagocytes in the liver. Liver macrophages consist of ontogenically distinct populations termed Kupffer cells and monocyte-derived macrophages. Kupffer cells are self-renewing, resident and principally non-migratory phagocytes, serving as sentinels for liver homeostasis. Liver injury triggers Kupffer cell activation, leading to inflammatory cytokine and chemokine release. This fosters the infiltration of monocytes into the liver, which give rise to large numbers of inflammatory monocyte-derived macrophages...
March 4, 2017: Journal of Hepatology
https://www.readbyqxmd.com/read/28254412/bromodomain-inhibitors-jq1-and-i-bet-762-as-potential-therapies-for-pancreatic-cancer
#16
Ana S Leal, Charlotte R Williams, Darlene B Royce, Patricia A Pioli, Michael B Sporn, Karen T Liby
Bromodomain inhibitors (JQ1 and I-BET 762) are a new generation of selective, small molecule inhibitors that target BET (bromodomain and extra terminal) proteins. By impairing their ability to bind to acetylated lysines on histones, bromodomain inhibitors interfere with transcriptional initiation and elongation. BET proteins regulate several genes responsible for cell cycle, apoptosis and inflammation. In this study, JQ1 and I-BET 762 decreased c-Myc and p-Erk 1/2 protein levels and inhibited proliferation in pancreatic cancer cells...
February 27, 2017: Cancer Letters
https://www.readbyqxmd.com/read/28217810/-effects-of-intrathecal-administration-of-am22-52-on-mechanical-allodynia-and-ccl2-expression-in-drg-in-bone-cancer-rats
#17
Ya-Juan Chen, Yuan-Hui Huo, Yanguo Hong
The pain peptide adrenomedullin (AM) plays a pivotal role in pathological pain. The present study was designed to investigate the effect of blockade of AM receptor on bone cancer pain (BCP) and its mechanism. BCP was developed by inoculation of Walker 256 mammary gland carcinoma cells in the tibia medullary cavity of Sprague Dawley rats. The selective AM receptor antagonist AM22-52 was administered intrathecally on 15 d after the inoculation. Quantitative real-time PCR was used to detect mRNA level of CC chemokine ligand 2 (CCL2) in dorsal root ganglion (DRG)...
February 25, 2017: Sheng Li Xue Bao: [Acta Physiologica Sinica]
https://www.readbyqxmd.com/read/28215642/ccl2-expression-correlates-with-snail-expression-and-affects-the-prognosis-of-patients-with-gastric-cancer
#18
Jia Zhang, Yan Yan, Xiaohai Cui, Jing Zhang, Ya Yang, Huajing Li, Hongpei Wu, Junhai Li, Li Wang, Min Li, Xu Liu, Jiansheng Wang, Xiaoyi Duan
We aim to explore the associations of CCL2 and Snail in gastric cancer to the clinicopathologic features and prognosis of gastric cancer (GC). In our study, the expression of CCL2 and Snail in clinical specimens of 178 GC patients was detected by immunohistochemistry. High expression of CCL2 and Snail were closely related to the clinicopathologic features. The results showed there is a link between CCL2 and Snail expression at protein levels (Pearson Χ2=40.751, P<0.001). The Kaplan-Meier survival analysis showed that CCL2 or Snail expression was correlated with 5-year survival rate (P<0...
March 2017: Pathology, Research and Practice
https://www.readbyqxmd.com/read/28212753/the-trail-induced-cancer-secretome-promotes-a-tumor-supportive-immune-microenvironment-via-ccr2
#19
Torsten Hartwig, Antonella Montinaro, Silvia von Karstedt, Alexandra Sevko, Silvia Surinova, Ankur Chakravarthy, Lucia Taraborrelli, Peter Draber, Elodie Lafont, Frederick Arce Vargas, Mona A El-Bahrawy, Sergio A Quezada, Henning Walczak
Tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL) is known for specifically killing cancer cells, whereas in resistant cancers, TRAIL/TRAIL-R can promote metastasis via Rac1 and PI3K. It remains unknown, however, whether and to what extent TRAIL/TRAIL-R signaling in cancer cells can affect the immune microenvironment. Here we show that TRAIL-triggered cytokine secretion from TRAIL-resistant cancer cells is FADD dependent and identify the TRAIL-induced secretome to drive monocyte polarization to myeloid-derived suppressor cells (MDSCs) and M2-like macrophages...
February 16, 2017: Molecular Cell
https://www.readbyqxmd.com/read/28202513/myeloid-cells-that-impair-immunotherapy-are-restored-in-melanomas-with-acquired-resistance-to-braf-inhibitors
#20
Shannon M Steinberg, Tamer B Shabaneh, Peisheng Zhang, Viktor Martyanov, Zhenghui Li, Brian T Malik, Tamara A Wood, Andrea Boni, Aleksey Molodtsov, Christina V Angeles, Tyler J Curiel, Michael L Whitfield, Mary Jo Turk
Acquired resistance to BRAF(V600E) inhibitors (BRAFi) in melanoma remains a common clinical obstacle, as is the case for any targeted drug therapy that can be developed given the plastic nature of cancers. Although there has been significant focus on the cancer cell-intrinsic properties of BRAFi resistance, the impact of BRAFi resistance on host immunity has not been explored. Here we provide preclinical evidence that resistance to BRAFi in an autochthonous mouse model of melanoma is associated with restoration of myeloid-derived suppressor cells (MDSC) in the tumor microenvironment, initially reduced by BRAFi treatment...
April 1, 2017: Cancer Research
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