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CCL2 AND CANCER

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https://www.readbyqxmd.com/read/28212753/the-trail-induced-cancer-secretome-promotes-a-tumor-supportive-immune-microenvironment-via-ccr2
#1
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
#2
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
#3
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
#4
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
#5
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
#6
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
#7
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
#8
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
#9
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
#10
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
#11
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
#12
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
#13
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
#14
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
#15
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 2017: Radiation Research
https://www.readbyqxmd.com/read/28041977/induction-of-the-mcp-chemokine-cluster-cascade-in-the-periphery-by-cancer-cell-derived-ccl3
#16
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...
March 28, 2017: Cancer Letters
https://www.readbyqxmd.com/read/28039457/tumor-associated-macrophages-promote-prostate-cancer-migration-through-activation-of-the-ccl22-ccr4-axis
#17
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
#18
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
#19
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
#20
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/GCIMP...
April 1, 2017: Cancer Letters
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