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CCL2 AND CANCER

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https://www.readbyqxmd.com/read/28344868/langerhans-cells-and-nk-cells-cooperate-in-the-inhibition-of-chemical-skin-carcinogenesis
#1
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
#2
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
#3
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
#4
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...
March 13, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28267621/targeting-hepatic-macrophages-to-treat-liver-diseases
#5
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 liver that give rise to large numbers of inflammatory monocyte-derived macrophages...
March 3, 2017: Journal of Hepatology
https://www.readbyqxmd.com/read/28254412/bromodomain-inhibitors-jq1-and-i-bet-762-as-potential-therapies-for-pancreatic-cancer
#6
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
#7
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
#8
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...
December 23, 2016: Pathology, Research and Practice
https://www.readbyqxmd.com/read/28212753/the-trail-induced-cancer-secretome-promotes-a-tumor-supportive-immune-microenvironment-via-ccr2
#9
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-which-acquire-resistance-to-braf-inhibitors
#10
Shannon M Steinberg, Tamer Shabaneh, Peisheng Zhang, Viktor Martyanov, Zhenghui Li, Brian Malik, Tammara Wood, Andrea Boni, Aleksey Molodtsov, Christina V Angeles, Tyler J Curiel, Michael Whitfield, Mary Jo Turk
Acquired resistance to BRAFV600E 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. While 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...
February 15, 2017: Cancer Research
https://www.readbyqxmd.com/read/28197374/tumor-derived-osteopontin-isoforms-cooperate-with-trp53-and-ccl2-to-promote-lung-metastasis
#11
Ioanna Giopanou, Ioannis Lilis, Vassilios Papaleonidopoulos, Theodora Agalioti, Nikolaos I Kanellakis, Nikolitsa Spiropoulou, Magda Spella, Georgios T Stathopoulos
The lungs are ubiquitous receptacles of metastases originating from various bodily tumors. Although osteopontin (SPP1) has been associated with tumor dissemination, the role of its isoforms in lung-directed metastasis is incompletely understood. We employed syngeneic mouse models of spontaneous and induced lung-targeted metastasis in C57BL/6 mice competent and deficient in both Spp1 alleles. Tumor-derived osteopontin expression was modulated using either stable anti-Spp1 RNA interference, or forced overexpression of intracellular and secreted Spp1 isoforms...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/28197019/inflammation-and-cancer-extra-and-intracellular-determinants-of-tumor-associated-macrophages-as-tumor-promoters
#12
REVIEW
Gabor J Szebeni, Csaba Vizler, Klara Kitajka, Laszlo G Puskas
One of the hallmarks of cancer-related inflammation is the recruitment of monocyte-macrophage lineage cells to the tumor microenvironment. These tumor infiltrating myeloid cells are educated by the tumor milieu, rich in cancer cells and stroma components, to exert functions such as promotion of tumor growth, immunosuppression, angiogenesis, and cancer cell dissemination. Our review highlights the ontogenetic diversity of tumor-associated macrophages (TAMs) and describes their main phenotypic markers. We cover fundamental molecular players in the tumor microenvironment including extra- (CCL2, CSF-1, CXCL12, IL-4, IL-13, semaphorins, WNT5A, and WNT7B) and intracellular signals...
2017: Mediators of Inflammation
https://www.readbyqxmd.com/read/28178994/doxycycline-attenuates-breast-cancer-related-inflammation-by-decreasing-plasma-lysophosphatidate-concentrations-and-inhibiting-nf-%C3%AE%C2%BAb-activation
#13
Xiaoyun Tang, Xianyan Wang, Yuan Y Zhao, Jonathan M Curtis, David N Brindley
BACKGROUND: We previously discovered that tetracyclines increase the expression of lipid phosphate phosphatases at the surface of cells. These enzymes degrade circulating lysophosphatidate and therefore doxycycline increases the turnover of plasma lysophosphatidate and decreases its concentration. Extracellular lysophosphatidate signals through six G protein-coupled receptors and it is a potent promoter of tumor growth, metastasis and chemo-resistance. These effects depend partly on the stimulation of inflammation that lysophosphatidate produces...
February 8, 2017: Molecular Cancer
https://www.readbyqxmd.com/read/28165033/micheliolide-provides-protection-of-mice-against-staphylococcus-aureus-and-mrsa-infection-by-down-regulating-inflammatory-response
#14
Xinru Jiang, Yuli Wang, Yifei Qin, Weigang He, Adel Benlahrech, Qingwen Zhang, Xin Jiang, Zhenhui Lu, Guang Ji, Yuejuan Zheng
A major obstacle to therapy in intensive care units is sepsis caused by severe infection. In recent years gram-positive (G(+)) bacteria, most commonly staphylococci, are thought to be the main pathogens. Micheliolide (MCL) was demonstrated to provide a therapeutic role in rheumatoid arthritis, inflammatory intestinal disease, colitis-associated cancer, and lipopolysaccharide (LPS, the main component of G(-) bacterial cell wall) induced septic shock. We proved here that MCL played an anti-inflammatory role in Staphylococcus aureus (S...
February 6, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28159925/mirna-1246-induces-pro-inflammatory-responses-in-mesenchymal-stem-stromal-cells-by-regulating-pka-and-pp2a
#15
Alexander Bott, Nese Erdem, Shalom Lerrer, Agnes Hotz-Wagenblatt, Christian Breunig, Khalid Abnaof, Angelika Wörner, Heike Wilhelm, Ewald Münstermann, Adit Ben-Baruch, Stefan Wiemann
The tumor microenvironment (TME) has an impact on breast cancer progression by creating a pro-inflammatory milieu within the tumor. However, little is known about the roles of miRNAs in cells of the TME during this process. We identified six putative oncomiRs in a breast cancer dataset, all strongly correlating with poor overall patient survival. Out of the six candidates, miR-1246 was upregulated in aggressive breast cancer subtypes and expressed at highest levels in mesenchymal stem/stroma cells (MSCs). Functionally, miR-1246 led to a p65-dependent increase in transcription and release of pro-inflammatory mediators IL-6, CCL2 and CCL5 in MSCs, and increased NF-κB activity...
January 31, 2017: Oncotarget
https://www.readbyqxmd.com/read/28157698/anti-cancer-effect-of-danshen-and-dihydroisotanshinone-i-on-prostate-cancer-targeting-the-crosstalk-between-macrophages-and-cancer-cells-via-inhibition-of-the-stat3-ccl2-signaling-pathway
#16
Ching-Yuan Wu, Yao-Hsu Yang, Yin-Yin Lin, Feng-Che Kuan, Yu-Shin Lin, Wei-Yu Lin, Ming-Yen Tsai, Jia-Jing Yang, Yu-Ching Cheng, Li-Hsin Shu, Ming-Chu Lu, Yun-Ju Chen, Kuan-Der Lee, Hong-Yo Kang
Danshen (Salvia miltiorrhiza Bunge) is widely used in traditional Chinese medicine. In our study, the in vivo protective effect of danshen in prostate cancer patients was validated through data from the National Health Insurance Research Database in Taiwan. In vitro, we discovered that dihydroisotanshinone I (DT), a bioactive compound present in danshen, can inhibit the migration of both androgen-dependent and androgen-independent prostate cancer cells. In addition, we noted that DT substantially inhibited the migratory ability of prostate cancer cells in both a macrophage-conditioned medium and macrophage/prostate cancer coculture medium...
February 1, 2017: Oncotarget
https://www.readbyqxmd.com/read/28143493/the-yin-yan-of-ccl2-a-minor-role-in-neutrophil-anti-tumor-activity-in-vitro-but-a-major-role-on-the-outgrowth-of-metastatic-breast-cancer-lesions-in-the-lung-in-vivo
#17
Nicole Lavender, Jinming Yang, Sheau-Chiann Chen, Jiqing Sai, C Andrew Johnson, Philip Owens, Gregory D Ayers, Ann Richmond
BACKGROUND: The role of the chemokine CCL2 in breast cancer is controversial. While CCL2 recruits and activates pro-tumor macrophages, it is also reported to enhance neutrophil-mediated anti-tumor activity. Moreover, loss of CCL2 in early development enhances breast cancer progression. METHODS: To clarify these conflicting findings, we examined the ability of CCL2 to alter naïve and tumor entrained neutrophil production of ROS, release of granzyme-B, and killing of tumor cells in multiple mouse models of breast cancer...
January 31, 2017: BMC Cancer
https://www.readbyqxmd.com/read/28125674/characterisation-of-immune-and-neuroinflammatory-changes-associated-with-chemotherapy-induced-peripheral-neuropathy
#18
Preet G S Makker, Samuel S Duffy, Justin G Lees, Chamini J Perera, Ryan S Tonkin, Oleg Butovsky, Susanna B Park, David Goldstein, Gila Moalem-Taylor
Chemotherapy-induced peripheral neuropathy (CIPN) and associated neuropathic pain is a debilitating adverse effect of cancer treatment. Current understanding of the mechanisms underpinning CIPN is limited and there are no effective treatment strategies. In this study, we treated male C57BL/6J mice with 4 cycles of either Paclitaxel (PTX) or Oxaliplatin (OXA) over a week and tested pain hypersensitivity and changes in peripheral immune responses and neuroinflammation on days 7 and 13 post 1st injection. We found that both PTX and OXA caused significant mechanical allodynia...
2017: PloS One
https://www.readbyqxmd.com/read/28125591/maternal-pre-pregnancy-obesity-is-associated-with-altered-placental-transcriptome
#19
Signe Altmäe, Maria Teresa Segura, Francisco J Esteban, Sabine Bartel, Pilar Brandi, Martin Irmler, Johannes Beckers, Hans Demmelmair, Carmen López-Sabater, Berthold Koletzko, Susanne Krauss-Etschmann, Cristina Campoy
Maternal obesity has a major impact on pregnancy outcomes. There is growing evidence that maternal obesity has a negative influence on placental development and function, thereby adversely influencing offspring programming and health outcomes. However, the molecular mechanisms underlying these processes are poorly understood. We analysed ten term placenta's whole transcriptomes in obese (n = 5) and normal weight women (n = 5), using the Affymetrix microarray platform. Analyses of expression data were carried out using non-parametric methods...
2017: PloS One
https://www.readbyqxmd.com/read/28095896/screening-for-potential-genes-associated-with-bone-overgrowth-after-mid-shaft-femur-fracture-in-a-rat-model
#20
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
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