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CCL2 AND CANCER

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https://www.readbyqxmd.com/read/28095896/screening-for-potential-genes-associated-with-bone-overgrowth-after-mid-shaft-femur-fracture-in-a-rat-model
#1
Chibing Liu, Yanting Liu, Weizhong Zhang, Xiuxin Liu
BACKGROUND: We investigated the underlying molecular mechanisms of bone overgrowth after femoral fracture by using high-throughput bioinformatics approaches. METHODS: The gene expression profile of GSE3298 (accession number) was obtained from the Gene Expression Omnibus database. Sixteen femoral growth plate samples, including nine samples without fracture and seven fracture samples for seven time points, were used for analysis. The Limma package was applied to identify differentially expressed genes (DEGs) between fractured and intact samples...
January 17, 2017: Journal of Orthopaedic Surgery and Research
https://www.readbyqxmd.com/read/28077301/mir-124-down-regulation-is-critical-for-cancer-associated-fibroblasts-enhanced-tumor-growth-of-oral-carcinoma
#2
Xia Li, Qinqiao Fan, Jinyun Li, Jing Song, Yangcong Gu
Cancer associated fibroblasts (CAFs) are known to be involved in initiation, progression and metastasis of various cancers. However, the molecular mechanism of how CAFs affects the biological function of oral cancer (OC) has not been fully-addressed. In this study, we demonstrated that miR-124 was downregulated in oral CAFs and oral cancer cells (OCCs) when compared with matched normal fibroblasts (NFs). Hypermethylation in the promoter region of miR-124 genes was accounted for its downregulation. Interestingly, CAFs but not NFs exerted promotion effect on OCCs cell proliferation, migration and tumor growth in CAFs/NFs-OCCs co-culture...
January 8, 2017: Experimental Cell Research
https://www.readbyqxmd.com/read/28077158/ccl2-driven-inflammation-increases-mammary-gland-stromal-density-and-cancer-susceptibility-in-a-transgenic-mouse-model
#3
Xuan Sun, Danielle J Glynn, Leigh J Hodson, Cecilia Huo, Kara Britt, Erik W Thompson, Lucy Woolford, Andreas Evdokiou, Jeffrey W Pollard, Sarah A Robertson, Wendy V Ingman
BACKGROUND: Macrophages play diverse roles in mammary gland development and breast cancer. CC-chemokine ligand 2 (CCL2) is an inflammatory cytokine that recruits macrophages to sites of injury. Although CCL2 has been detected in human and mouse mammary epithelium, its role in regulating mammary gland development and cancer risk has not been explored. METHODS: Transgenic mice were generated wherein CCL2 is driven by the mammary epithelial cell-specific mouse mammary tumour virus 206 (MMTV) promoter...
January 11, 2017: Breast Cancer Research: BCR
https://www.readbyqxmd.com/read/28054838/il-6-mediates-macrophage-infiltration-after-irradiation-via-up-regulation-of-ccl2-ccl5-in-non-small-cell-lung-cancer
#4
Xin Wang, Xiaodong Yang, Ying Tsai, Li Yang, Kuang-Hsiang Chuang, Peter C Keng, Soo Ok Lee, Yuhchyau Chen
Radiotherapy is effective in reducing primary tumors, however, it may enhance macrophage infiltration to tumor sites, accelerating tumor progression in several ways. We investigated whether radiation can increase macrophage infiltration into non-small cell lung carcinoma (NSCLC) cells. Analysis of in vitro macrophage (differentiated THP-1 cells) migration to either nonirradiated or irradiated tumor cells showed increased migration to the irradiated tumor cells. Because the IL-6 levels in A549 and H157 cells were significantly increased after irradiation, we then investigated whether this increased IL-6 level contributes to radiation-induced macrophage migration...
January 5, 2017: Radiation Research
https://www.readbyqxmd.com/read/28041977/induction-of-the-mcp-chemokine-cluster-cascade-in-the-periphery-by-cancer-cell-derived-ccl3
#5
Elena Farmaki, Vimala Kaza, Athanasios G Papavassiliou, Ioulia Chatzistamou, Hippokratis Kiaris
The induction of localized pro-inflammatory niches in the periphery is instrumental in metastasis. In order to better understand how tumors engage distal sites and activate a pro-inflammatory response we utilized syngeneic breast cancers as a model and showed that soluble factors from the neoplastic epithelium activate the expression of the monocyte chemoattractive protein (MCP) chemokines of the mouse 11C cluster that include Ccl1, Ccl2, Ccl7, Ccl8, Ccl11 and Ccl12. Tissues such as the lungs and the brain, that are more prone to colonization by breast cancer cells, were more sensitive to MCP cluster chemokine induction than others such as the liver...
December 29, 2016: Cancer Letters
https://www.readbyqxmd.com/read/28039457/tumor-associated-macrophages-promote-prostate-cancer-migration-through-activation-of-the-ccl22-ccr4-axis
#6
Aerken Maolake, Kouji Izumi, Kazuyoshi Shigehara, Ariunbold Natsagdorj, Hiroaki Iwamoto, Suguru Kadomoto, Yuta Takezawa, Kazuaki Machioka, Kazutaka Narimoto, Mikio Namiki, Wen-Jye Lin, Guzailinuer Wufuer, Atsushi Mizokami
Previous studies have found that tumor-associated macrophages (TAMs) promote cancer progression. We previously reported that TAMs promote prostate cancer metastasis via activation of the CCL2-CCR2 axis. The CCR4 (receptor of CCL17 and CCL22) expression level in breast cancer was reported to be associated with lung metastasis. The aim of this study was to elucidate the role of CCR2 and CCR4 in prostate cancer progression. CCR2 and CCR4 were expressed in human prostate cancer cell lines and prostate cancer tissues...
December 26, 2016: Oncotarget
https://www.readbyqxmd.com/read/28032600/the-function-of-cancer-shed-gangliosides-in-macrophage-phenotype-involvement-with-angiogenesis
#7
Tae-Wook Chung, Hee-Jung Choi, Mi-Ju Park, Hee-Jin Choi, Syng-Ook Lee, Keuk-Jun Kim, Cheorl-Ho Kim, Changwan Hong, Kyun-Ha Kim, Myungsoo Joo, Ki-Tae Ha
Tumor-derived gangliosides in the tumor microenvironment are involved in the malignant progression of cancer. However, the molecular mechanisms underlying the effects of gangliosides shed from tumors on macrophage phenotype remain unknown. Here, we showed that ganglioside GM1 highly induced the activity and expression of arginase-1 (Arg-1), a major M2 macrophage marker, compared to various gangliosides in bone marrow-derived macrophages (BMDM), peritoneal macrophages and Raw264.7 macrophage cells. We found that GM1 bound to macrophage mannose receptor (MMR/CD206) and common gamma chain (γc)...
December 10, 2016: Oncotarget
https://www.readbyqxmd.com/read/28025994/the-analgesic-effect-of-rolipram-is-associated-with-the-inhibition-of-the-activation-of-the-spinal-astrocytic-jnk-ccl2-pathway-in-bone-cancer-pain
#8
Chi-Hua Guo, Lu Bai, Huang-Hui Wu, Jing Yang, Guo-Hong Cai, Xin Wang, Sheng-Xi Wu, Wei Ma
Bone cancer pain (BCP) is one of the most difficult and intractable tasks for pain management, which is associated with spinal 'neuron-astrocytic' activation. The activation of the c-Jun N-terminal kinase (JNK)/chemokine (C-C motif) ligand (CCL2) signaling pathway has been reported to be critical for neuropathic pain. Rolipram (ROL), a selective phosphodiesterase 4 inhibitor, possesses potent anti-inflammatory and anti-nociceptive activities. The present study aimed to investigate whether the intrathecal administration of ROL has an analgesic effect on BCP in rats, and to assess whether the inhibition of spinal JNK/CCL2 pathway and astrocytic activation are involved in the analgesic effects of ROL...
November 2016: International Journal of Molecular Medicine
https://www.readbyqxmd.com/read/28007636/inflammatory-landscape-of-human-brain-tumors-reveals-an-nf%C3%AE%C2%BAb-dependent-cytokine-pathway-associated-with-mesenchymal-glioblastoma
#9
Alfeu Zanotto-Filho, Rosângela Mayer Gonçalves, Karina Klafke, Priscila Oliveira de Souza, Fabiane Cristine Dillenburg, Luigi Carro, Daniel Pens Gelain, José Cláudio Fonseca Moreira
The tumor microenvironment is being increasingly recognized as a key factor in cancer aggressiveness. In this study, we characterized the inflammatory gene signatures altered in glioma cell lines and tumor specimens of differing histological and molecular subtypes. The results showed that glioblastoma multiforme (GBM) shows upregulation of a subset of inflammatory genes when compared to astrocytomas and oligodendrogliomas. With molecular subtypes of GBM, the expression of inflammatory genes is heterogeneous, being enriched in mesenchymal and downregulated in Proneural and GCIMP...
December 20, 2016: Cancer Letters
https://www.readbyqxmd.com/read/27980102/blocking-the-ccl2-ccr2-axis-using-ccl2-neutralizing-antibody-is-an-effective-therapy-for-hepatocellular-cancer-in-a-mouse-model
#10
Kun-Yu Teng, Jianfeng Han, Xiaoli Zhang, Shu-Hao Hsu, Shun He, Nissar Wani, Juan Barajas, Linda A Snyder, Wendy L Frankel, Michael A Caligiuri, Samson T Jacob, Jianhua Yu, Kalpana Ghoshal
Hepatocellular carcinoma (HCC), a deadly disease, commonly arises in the setting of chronic inflammation. C-C motif chemokine ligand2 (CCL2/MCP1), a chemokine that recruits CCR2-positive immune cells to promote inflammation, is highly upregulated in HCC patients. Here, we examined the therapeutic efficacy of CCL2-CCR2 axis inhibitors against hepatitis and HCC in the miR-122 knockout (aka KO) mouse model. This mouse model displays upregulation of hepatic CCL2 expression, which correlates with hepatitis that progress to HCC with age...
December 15, 2016: Molecular Cancer Therapeutics
https://www.readbyqxmd.com/read/27926736/structure-of-cc-chemokine-receptor-2-with-orthosteric-and-allosteric-antagonists
#11
Yi Zheng, Ling Qin, Natalia V Ortiz Zacarías, Henk de Vries, Gye Won Han, Martin Gustavsson, Marta Dabros, Chunxia Zhao, Robert J Cherney, Percy Carter, Dean Stamos, Ruben Abagyan, Vadim Cherezov, Raymond C Stevens, Adriaan P IJzerman, Laura H Heitman, Andrew Tebben, Irina Kufareva, Tracy M Handel
CC chemokine receptor 2 (CCR2) is one of 19 members of the chemokine receptor subfamily of human class A G-protein-coupled receptors. CCR2 is expressed on monocytes, immature dendritic cells, and T-cell subpopulations, and mediates their migration towards endogenous CC chemokine ligands such as CCL2 (ref. 1). CCR2 and its ligands are implicated in numerous inflammatory and neurodegenerative diseases including atherosclerosis, multiple sclerosis, asthma, neuropathic pain, and diabetic nephropathy, as well as cancer...
December 15, 2016: Nature
https://www.readbyqxmd.com/read/27888616/ccl2-egf-positive-feedback-loop-between-cancer-cells-and-macrophages-promotes-cell-migration-and-invasion-in-head-and-neck-squamous-cell-carcinoma
#12
Lu Gao, Feng-Qin Wang, Hui-Min Li, Jie-Gang Yang, Jian-Gang Ren, Ke-Fei He, Bing Liu, Wei Zhang, Yi-Fang Zhao
Head and neck squamous cell carcinoma (HNSCC) represents the most frequent malignancy in the head and neck region, and the survival rate has not been improved significantly over the past three decades. It has been reported the infiltrated macrophages contribute to the malignant progression of HNSCC. However, the crosstalk between macrophages and cancer cells remains poorly understood. In the present study, we explored interactions between monocytes/macrophages and HNSCC cells by establishing the direct co-culture system, and found that the crosstalk promoted the migration and invasion of cancer cells by enhancing the invadopodia formation through a CCL2/EGF positive feedback loop...
November 23, 2016: Oncotarget
https://www.readbyqxmd.com/read/27853653/dense-breast-tissue-in-postmenopausal-women-is-associated-with-a-pro-inflammatory-microenvironment-in-vivo
#13
Annelie Abrahamsson, Anna Rzepecka, Thobias Romu, Magnus Borga, Olof Dahlqvist Leinhard, Peter Lundberg, Johan Kihlberg, Charlotta Dabrosin
Inflammation is one of the hallmarks of carcinogenesis. High mammographic density has been associated with increased risk of breast cancer but the mechanisms behind are poorly understood. We evaluated whether breasts with different mammographic densities exhibited differences in the inflammatory microenvironment. Postmenopausal women attending the mammography-screening program were assessed having extreme dense, n = 20, or entirely fatty breasts (nondense), n = 19, on their regular mammograms. Thereafter, the women were invited for magnetic resonance imaging (MRI), microdialysis for the collection of extracellular molecules in situ and a core tissue biopsy for research purposes...
2016: Oncoimmunology
https://www.readbyqxmd.com/read/27853634/dynamic-alterations-of-bone-marrow-cytokine-landscape-of-myelodysplastic-syndromes-patients-treated-with-5-azacytidine
#14
Alena Moudra, Sona Hubackova, Veronika Machalova, Marketa Vancurova, Jiri Bartek, Milan Reinis, Zdenek Hodny, Anna Jonasova
Myelodysplastic syndromes (MDS) represent a heterogeneous group of clonal stem cell disorders characterized by ineffective hematopoiesis frequently progressing into acute myeloid leukemia (AML), with emerging evidence implicating aberrant bone marrow (BM) microenvironment and inflammation-related changes. 5-azacytidine (5-AC) represents standard MDS treatment. Besides inhibiting DNA/RNA methylation, 5-AC has been shown to induce DNA damage and apoptosis in vitro. To provide insights into in vivo effects, we assessed the proinflammatory cytokines alterations during MDS progression, cytokine changes after 5-AC, and contribution of inflammatory comorbidities to the cytokine changes in MDS patients...
2016: Oncoimmunology
https://www.readbyqxmd.com/read/27852031/increasing-the-efficacy-of-radiotherapy-by-modulating-the-ccr2-ccr5-chemokine-axes
#15
Kelli A Connolly, Brian A Belt, Nathania M Figueroa, Aditi Murthy, Ankit Patel, Minsoo Kim, Edith M Lord, David C Linehan, Scott A Gerber
Although radiotherapy (RT) is widely used to control tumor growth across many cancer types, there is a relatively high incidence of RT failure exhibited by tumor recurrence, therefore a clear need exists to achieve improved effectiveness of RT. The RT-elicited immune response largely impacts the efficacy of RT and includes immune cells that kill tumor cells, but also immunosuppressive cells, which dampen anti-tumor immunity. Using murine models in which syngeneic tumor cell lines (Colon38, Glioma261, Line1) are grown intramuscularly and treated with 15 Gy local RT, we assessed the effects of RT on both the systemic and intratumoral immune response...
November 11, 2016: Oncotarget
https://www.readbyqxmd.com/read/27822063/the-accumulation-of-macrophages-attenuates-the-effect-of-recombinant-human-endostatin-on-lung-cancer
#16
Yanyang Liu, Li Tu, Li Wang, Jianlin Long, Jiantao Wang, Yuyi Wang, Feng Luo, Dan Cao
BACKGROUND: Although anti-angiogenic therapy is widely applied clinically, its efficacy has been less than expected. Screening for regulatory factors and sensitive indicators to define the effectiveness of these drugs is required. Through a retrospective study of clinical data, we found that patients with a higher peripheral monocyte-to-lymphocyte ratio (MLR) obtained less benefit from recombinant human endostatin (rhES, Endostar(®)), an anti-angiogenic drug, in lung cancer. Because MLR is positively correlated with macrophage count in tumors, this result suggests that macrophages may influence the effectiveness of rhES therapy in lung cancer...
2016: OncoTargets and Therapy
https://www.readbyqxmd.com/read/27820834/ccl2-ccr2-regulates-the-tumor-microenvironment-in-her-2-neu-driven-mammary-carcinomas-in-mice
#17
Xuguang Chen, Yunyue Wang, David Nelson, Sara Tian, Erin Mulvey, Bhumi Patel, Ilaria Conti, Juan Jaen, Barrett J Rollins
Chronic inflammation is a hallmark of cancer. Inflammatory chemokines, such as C-C chemokine ligand 2 (CCL2), are often present in tumors but their roles in cancer initiation and maintenance are not clear. Here we report that CCL2 promotes mammary carcinoma development in a clinically relevant murine model of breast cancer. Targeted disruption of Ccl2 slowed the growth of activated Her2/neu-driven mammary tumors and prolonged host survival. Disruption of Ccl2 was associated with a decrease in the development and mobilization of endothelial precursor cells (EPCs) which can contribute to tumor neovascularization...
2016: PloS One
https://www.readbyqxmd.com/read/27812285/a-multifaceted-role-for-myd88-dependent-signaling-in-progression-of-murine-mammary-carcinoma
#18
Mary J Higgins, Antonio Serrano, Kofi Y Boateng, Victoria A Parsons, Tiffany Phuong, Alyssa Seifert, Jacob M Ricca, Kyle C Tucker, Alec S Eidelman, Maureen A Carey, Robert A Kurt
Previous data obtained in our laboratory suggested that there may be constitutive signaling through the myeloid differentiation primary response gene 88 (Myd88)-dependent signaling cascade in murine mammary carcinoma. Here, we extended these findings by showing that, in the absence of an added Toll-like receptor (TLR) agonist, the myddosome complex was preformed in 4T1 tumor cells, and that Myd88 influenced cytoplasmic extracellular signal-regulated kinase (Erk)1/Erk2 levels, nuclear levels of nuclear factor-kappaB (NFκB) and signal transducer and activator of transcription 5 (STAT5), tumor-derived chemokine (C-C motif) ligand 2 (CCL2) expression, and in vitro and in vivo tumor growth...
2016: Breast Cancer: Basic and Clinical Research
https://www.readbyqxmd.com/read/27807511/tumor-associated-macrophages-in-kidney-cancer
#19
REVIEW
Olga V Kovaleva, Daria V Samoilova, Maria S Shitova, Alexei Gratchev
Tumor associated macrophages (TAMs) are an important element of tumor stroma. They originate from blood monocytes attracted by chemokines and cytokines produced by tumor cells and, being instructed by tumor microenvironment, develop into potent tumor-supporting cell population. TAMs were demonstrated to directly stimulate tumor cell proliferation and to promote angiogenesis. Further TAMs provide for efficient immune escape by producing immunosuppressive cytokines and facilitate tumor dissemination by producing extracellular matrix remodeling enzymes...
2016: Analytical Cellular Pathology (Amsterdam)
https://www.readbyqxmd.com/read/27779470/tumour-associated-macrophages-influence-canine-mammary-cancer-stem-like-cells-enhancing-their-pro-angiogenic-properties
#20
A Rybicka, C Eyileten, B Taciak, J Mucha, K Majchrzak, E Hellmen, M Krol
Cancer stem-like cells as cells with ability to self-renewal and potential to differentiate into various types of cells are known to be responsible for tumour initiation, recurrence and drug resistance. Hence a comprehensive research is concentrated on discovering cancer stem-like cells biology and interdependence between them and other cells. The aim of our study was to evaluate the impact of macrophages on cancer stem-like cells in canine mammary carcinomas. As recent studies indicated presence of macrophages in cancer environment stimulates cancer cells into more motile and invasive cells by acquisition of macrophage phenotypes...
August 2016: Journal of Physiology and Pharmacology: An Official Journal of the Polish Physiological Society
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