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CCL2 AND CANCER

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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
#1
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
#2
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
#3
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
#4
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
#5
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
#6
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
#7
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
#8
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
#9
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
https://www.readbyqxmd.com/read/27770720/inhibitory-effects-of-flavonoids-extracted-from-nepalese-propolis-on-the-lps-signaling-pathway
#10
Megumi Funakoshi-Tago, Kentaro Ohsawa, Toshiyuki Ishikawa, Fumika Nakamura, Fumihito Ueda, Yuji Narukawa, Fumiyuki Kiuchi, Hiroomi Tamura, Kenji Tago, Tadashi Kasahara
Flavonoids, particularly those derived from plants, harbor biological effects such as anti-inflammation and the inhibition of cancer progression. In the present study, we investigated the effects of 10 kinds of flavonoids isolated from Nepalese propolis on the LPS signaling pathway in order to clarify their anti-inflammatory activities. Five types of flavonoids: isoliquiritigenin, chrysin, 3',4'-dihydroxy-4-methoxydalbergione, 4-methoxydalbergion, and cearoin, markedly inhibited inflammatory responses including LPS-induced NO production by suppressing the expression of iNOS mRNA and LPS-induced mRNA expression of TNFα and CCL2...
October 19, 2016: International Immunopharmacology
https://www.readbyqxmd.com/read/27766226/nf-k%C3%AE-activation-in-u266-cells-on-mesenchymal-stem-cells
#11
Sara Zahedi, Karim Shamsasenjan, Aliakbar Movassaghpour, Parvin Akbarzadehlaleh
Purpose: Mesenchymal Stem Cells (MSCs) are one of the essential members of Bone Marrow (BM) microenvironment and the cells affect normal and malignant cells in BM milieu. One of the most important hematological malignancies is Multiple Myeloma (MM). Numerous studies reported various effects of MSCs on myeloma cells. MSCs initiate various signaling pathways in myeloma cells, particularly NF-kβ. NF-kβ signaling pathway plays pivotal role in the survival, proliferation and resistance of myeloma cells to the anticancer drugs, therefore this pathway can be said to be a vital target for cancer therapy...
September 2016: Advanced Pharmaceutical Bulletin
https://www.readbyqxmd.com/read/27750106/breast-cancer-osteomimicry-and-its-role-in-bone-specific-metastasis-an%C3%A2-integrative-systematic-review-of-preclinical-evidence
#12
REVIEW
Olugbenga Awolaran, Susan A Brooks, Verna Lavender
Metastasis accounts for most of the deaths from breast cancer and the preference of invasive breast cancer metastasising to bone has been widely reported. However, the biological basis of breast cancer osteotropism is not fully understood. This paper provides, for the first time, an integrative, systematic review of evidence of molecular factors that have functional roles in the homing of metastatic breast cancer to the bone. Pubmed, Web of Science and EBSCOhost were searched using keywords and synonyms for molecular, metastasis, breast cancer and bone to identify articles published between January 2004 and August 2016...
December 2016: Breast: Official Journal of the European Society of Mastology
https://www.readbyqxmd.com/read/27728798/senescence-and-cancer-in-the-name-of-immunosuppression
#13
Susana Llanos, Manuel Serrano
Senescent cells and cancer cells recruit immunosuppressive myeloid cells. In this issue of Cancer Cell, Eggert et al. report that senescent cells recruit immature myeloid cells (iMCs) through the secretion of the CCL2 cytokine and that these iMCs have pro- or anti-tumorigenic activities, depending on the cellular context.
October 10, 2016: Cancer Cell
https://www.readbyqxmd.com/read/27680685/ccr2-influences-t-regulatory-cell-migration-to-tumors-and-serves-as-a-biomarker-of-cyclophosphamide-sensitivity
#14
Pierre-Louis Loyher, Juliette Rochefort, Camille Baudesson de Chanville, Pauline Hamon, Géraldine Lescaille, Chloé Bertolus, Maude Guillot-Delost, Matthew F Krummel, François M Lemoine, Christophe Combadière, Alexandre Boissonnas
The CCL2 chemokine receptor CCR2 drives cancer by mediating the recruitment of monocytes and myeloid-derived suppressor cells to the tumor microenvironment. In this study, we extend the significance of CCR2 in this setting by identifying a new role for it in mediating recruitment of CD4(+) T regulatory cells (Treg). Following tumor initiation, an expanded population of CCR2(+) Tregs required CCR2 expression to traffic between draining lymph nodes (dLN) and the tumor. This Treg subset was enriched in the fraction of tumor antigen-specific cells in the dLN, where they displayed an activated immunosuppressive phenotype...
September 28, 2016: Cancer Research
https://www.readbyqxmd.com/read/27666332/ccl2-as-a-potential-therapeutic-target-for-clear-cell-renal-cell-carcinoma
#15
Ryuichiro Arakaki, Toshinari Yamasaki, Toru Kanno, Noboru Shibasaki, Hiromasa Sakamoto, Noriaki Utsunomiya, Takayuki Sumiyoshi, Shinsuke Shibuya, Tatsuaki Tsuruyama, Eijiro Nakamura, Osamu Ogawa, Tomomi Kamba
We previously reported that the pVHL-atypical PKC-JunB pathway contributed to promotion of cell invasiveness and angiogenesis in clear cell renal cell carcinoma (ccRCC), and we detected chemokine (C-C motif) ligand-2 (CCL2) as one of downstream effectors of JunB. CCL2 plays a critical role in tumorigenesis in other types of cancer, but its role in ccRCC remains unclear. In this study, we investigated the roles and therapeutic potential of CCL2 in ccRCC. Immunohistochemical analysis of CCL2 expression for ccRCC specimens showed that upregulation of CCL2 expression correlated with clinical stage, overall survival, and macrophage infiltration...
September 26, 2016: Cancer Medicine
https://www.readbyqxmd.com/read/27622061/stromal-ccr6-drives-tumor-growth-in-a-murine-transplantable-colon-cancer-through-recruitment-of-tumor-promoting-macrophages
#16
Bisweswar Nandi, Mia Shapiro, Mehmet K Samur, Christine Pai, Natasha Y Frank, Charles Yoon, Rao H Prabhala, Nikhil C Munshi, Jason S Gold
Interactions between the inflammatory chemokine CCL20 and its receptor CCR6 have been implicated in promoting colon cancer; however, the mechanisms behind this effect are poorly understood. We have previously demonstrated that deficiency of CCR6 is associated with decreased tumor macrophage accumulation in a model of sporadic intestinal tumorigenesis. In this study, we aimed to determine the role of stromal CCR6 expression in a murine syngeneic transplantable colon cancer model. We show that deficiency of host CCR6 is associated with decreased growth of syngeneic CCR6-expressing colon cancers...
August 2016: Oncoimmunology
https://www.readbyqxmd.com/read/27541266/reprogramming-of-normal-fibroblasts-into-cancer-associated-fibroblasts-by-mirnas-mediated-ccl2-vegfa-signaling
#17
Hua Shen, Xiaobo Yu, Fengming Yang, Zhihua Zhang, Jianxin Shen, Jin Sun, Swati Choksi, Siriporn Jitkaew, Yongqian Shu
Cancer-associated fibroblasts (CAFs), the most common constituent of the tumor stoma, are known to promote tumor initiation, progression and metastasis. However, the mechanism of how cancer cells transform normal fibroblasts (NFs) into CAFs is largely unknown. In this study, we determined the contribution of miRNAs in the transformation of NFs into CAFs. We found that miR-1 and miR-206 were down-regulated, whereas miR-31 was up-regulated in lung CAFs when compared with matched NFs. Importantly, modifying the expression of these three deregulated miRNAs induced a functional conversion of NFs into CAFs and vice versa...
August 2016: PLoS Genetics
https://www.readbyqxmd.com/read/27530322/ccl2-produced-by-the-glioma-microenvironment-is-essential-for-the-recruitment-of-regulatory-t-cells-and-myeloid-derived-suppressor-cells
#18
Alan L Chang, Jason Miska, Derek A Wainwright, Mahua Dey, Claudia V Rivetta, Dou Yu, Deepak Kanojia, Katarzyna C Pituch, Jian Qiao, Peter Pytel, Yu Han, Meijing Wu, Lingjiao Zhang, Craig M Horbinski, Atique U Ahmed, Maciej S Lesniak
In many aggressive cancers, such as glioblastoma multiforme, progression is enabled by local immunosuppression driven by the accumulation of regulatory T cells (Treg) and myeloid-derived suppressor cells (MDSC). However, the mechanistic details of how Tregs and MDSCs are recruited in various tumors are not yet well understood. Here we report that macrophages and microglia within the glioma microenvironment produce CCL2, a chemokine that is critical for recruiting both CCR4(+) Treg and CCR2(+)Ly-6C(+) monocytic MDSCs in this disease setting...
October 1, 2016: Cancer Research
https://www.readbyqxmd.com/read/27513864/intricate-macrophage-colorectal-cancer-cell-communication-in-response-to-radiation
#19
Ana T Pinto, Marta L Pinto, Sérgia Velho, Marta T Pinto, Ana P Cardoso, Rita Figueira, Armanda Monteiro, Margarida Marques, Raquel Seruca, Mário A Barbosa, Marc Mareel, Maria J Oliveira, Sónia Rocha
Both cancer and tumour-associated host cells are exposed to ionizing radiation when a tumour is subjected to radiotherapy. Macrophages frequently constitute the most abundant tumour-associated immune population, playing a role in tumour progression and response to therapy. The present work aimed to evaluate the importance of macrophage-cancer cell communication in the cellular response to radiation. To address this question, we established monocultures and indirect co-cultures of human monocyte-derived macrophages with RKO or SW1463 colorectal cancer cells, which exhibit higher and lower radiation sensitivity, respectively...
2016: PloS One
https://www.readbyqxmd.com/read/27486225/a-novel-small-molecule-activator-of-nuclear-receptor-shp-inhibits-hcc-cell-migration-via-suppressing-ccl2
#20
Zhihong Yang, Angela N Koehler, Li Wang
Small heterodimer partner (SHP, NR0B2) is a nuclear orphan receptor without endogenous ligands. Due to its crucial inhibitory role in liver cancer, it is of importance to identify small molecule agonists of SHP. As such, we initiated a probe discovery effort to identify compounds capable of modulating SHP function. First, we performed binding assays using small molecule microarrays (SMM) and discovered 5-(diethylsulfamoyl)-3-hydroxynaphthalene-2-carboxylic acid (DSHN) as a novel activator of SHP. DSHN transcriptionally activated Shp mRNA, but also stabilized the SHP protein by preventing its ubiquitination and degradation...
October 2016: Molecular Cancer Therapeutics
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