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CCL2 AND CANCER

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https://www.readbyqxmd.com/read/28819453/s100-spect-uncovers-cellular-and-molecular-events-of-pre-metastatic-niche-formation-and-following-organ-specific-cancer-metastasis
#1
EDITORIAL
Masakiyo Sakaguchi
Great progress has been made in in vivo imaging for cancer metastasis. Eisenblaetter et al. developed an innovative S100A8/A9-specific single photon emission computed tomography (SPECT) probe for imaging and succeeded in detecting the metastatic organ favored by the cancer before the cancer arrival. By utilizing this advanced method, researchers have also found that cancer-derived monocytes are the main source of the abundant production of S100A8/A9 in the pre-metastatic area. The CCL2-CCR2 axis is associated with S100A8/A9 production...
2017: Theranostics
https://www.readbyqxmd.com/read/28818997/ccr2-3-utr-functions-as-a-competing-endogenous-rna-to-inhibit-breast-cancer-metastasis
#2
Jinhang Hu, Xiaoman Li, Xinwei Guo, Qianqian Guo, Chenxi Xiang, Zhiting Zhang, Yingying Xing, Tao Xi, Lufeng Zheng
Diverse RNA transcripts acting as competing endogenous RNAs (ceRNAs) can co-regulate each other's expression by competing for shared microRNAs. CCR2 protein, the receptor of CCL2, is implicated in cancer progression. However, our results showed that higher CCR2 mRNA level was remarkably associated with prolonged survival of breast cancer patients. The conflicting results prompt us to study the non-coding function of CCR2 mRNA. We indicated that CCR2 3'UTR inhibited MDA-MB-231 and MCF-7 cells metastasis by repressing EMT in vitro and suppressed breast cancer metastasis in vivo Mechanistically, CCR2 3'UTR modulated RhoGAP protein STARD13 expression via acting as a STARD13 ceRNA in a microRNA-dependent and protein coding-independent manner...
August 17, 2017: Journal of Cell Science
https://www.readbyqxmd.com/read/28811968/il-32%C3%AE-induced-inflammation-constitutes-a-link-between-obesity-and-colon-cancer
#3
Victoria Catalán, Javier Gómez-Ambrosi, Amaia Rodríguez, Beatriz Ramírez, Victor A Ortega, José Luis Hernández-Lizoain, Jorge Baixauli, Sara Becerril, Fernando Rotellar, Víctor Valentí, Rafael Moncada, Camilo Silva, Javier Salvador, Gema Frühbeck
Growing evidence indicates that adipose tissue inflammation is an important mechanism whereby obesity promotes cancer risk and progression. Since IL-32 is an important inflammatory and remodeling factor in obesity and is also related to colon cancer (CC) development, the aim of this study was to explore whether IL-32 could function as an inflammatory factor in human obesity-associated CC promoting a microenvironment favorable for tumor growth. Samples obtained from 84 subjects [27 lean (LN) and 57 obese (OB)] were used in the study...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/28807849/danshen-improves-survival-of-patients-with-colon-cancer-and-dihydroisotanshinone-i-inhibit-the-proliferation-of-colon-cancer-cells-via-apoptosis-and-skp2-signaling-pathway
#4
Yin-Yin Lin, I-Yun Lee, Wen-Shih Huang, Yu-Shin Lin, Feng-Che Kuan, Li-Hsin Shu, Yu-Ching Cheng, Yao-Hsu Yang, Ching-Yuan Wu
ETHNOPHARMACOLOGICAL RELEVANCE: Danshen (Salvia miltiorrhiza Bunge) is widely used in traditional Chinese medicine. However, it's definite clinical effect and mechanism on colon carcinoma is unclear. AIM OF THE STUDY: To test the hypothesis that the protective effect of danshen on colon cancer and discover the bioactive compounds through in vitro study. MATERIALS AND METHODS: We conducted a nationwide cohort study by using population-based data from the Taiwan National Health Insurance Research Database (NHIRD)...
August 11, 2017: Journal of Ethnopharmacology
https://www.readbyqxmd.com/read/28794879/human-papillomavirus-driven-immune-deviation-challenge-and-novel-opportunity-for-immunotherapy
#5
REVIEW
Sigrun Smola, Connie Trimble, Peter L Stern
It is now recognized that the immune system can be a key component of restraint and control during the neoplastic process. Human papillomavirus (HPV)-associated cancers of the anogenital tract and oropharynx represent a significant clinical problem but there is a clear opportunity for immune targeting of the viral oncogene expression that drives cancer development. However, high-risk HPV infection of the target epithelium and the expression of the E6/E7 oncogenes can lead to early compromise of the innate immune system (loss of antigen-presenting cells) facilitating viral persistence and increased risk of cancer...
June 2017: Therapeutic Advances in Vaccines
https://www.readbyqxmd.com/read/28790030/notch-shapes-the-innate-immunophenotype-in-breast-cancer
#6
Qiang Shen, Brenda Cohen, Weiyue Zheng, Ramtin Rahbar, Bernard Martin, Kiichi Murakami, Sara Lamorte, Patrycja Thompson, Hal Berman, Juan Carlos Zúñiga-Pflücker, Pamela S Ohashi, Michael Reedijk
Notch activation, which is associated with basal-like breast cancer (BLBC), normally directs tissue patterning, suggesting that it may shape the tumor microenvironment (TME). Here we show that Notch in tumor cells regulates the expression of two powerful pro-inflammatory cytokines, IL1β and CCL2, and the recruitment of tumor-associated macrophages (TAMs). Notch also regulates TGFβ-mediated activation of tumor cells by TAMs, closing a Notch-dependent paracrine signaling loop between these two cell types. We use a novel mouse model in which Notch can be regulated in spontaneous mammary carcinoma to confirm that IL1β and CCL2 production, and macrophage recruitment are Notch-dependent...
August 8, 2017: Cancer Discovery
https://www.readbyqxmd.com/read/28757590/tanshinone-iia-inhibits-epithelial-mesenchymal-transition-in-bladder-cancer-cells-via-modulation-of-stat3-ccl2-signaling
#7
Sung-Ying Huang, Shu-Fang Chang, Kuan-Fu Liao, Sheng-Chun Chiu
Tanshinone IIA (Tan-IIA) is an extract from the widely used traditional Chinese medicine (TCM) Danshen (Salvia miltiorrhiza), and has been found to attenuate the proliferation of bladder cancer (BCa) cells (The IC50 were: 5637, 2.6 μg/mL; BFTC, 2 μg/mL; T24, 2.7 μg/mL, respectively.). However, the mechanism of the effect of Tan-IIA on migration inhibition of BCa cells remains unclear. This study investigates the anti-metastatic effect of Tan-IIA in human BCa cells and clarifies its molecular mechanism. Three human BCa cell lines, 5637, BFTC and T24, were used for subsequent experiments...
July 25, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28754746/tumor-derived-exosomes-modulate-pd-l1-expression-in-monocytes
#8
Franziska Haderk, Ralph Schulz, Murat Iskar, Laura Llaó Cid, Thomas Worst, Karolin V Willmund, Angela Schulz, Uwe Warnken, Jana Seiler, Axel Benner, Michelle Nessling, Thorsten Zenz, Maria Göbel, Jan Dürig, Sven Diederichs, Jérôme Paggetti, Etienne Moussay, Stephan Stilgenbauer, Marc Zapatka, Peter Lichter, Martina Seiffert
In chronic lymphocytic leukemia (CLL), monocytes and macrophages are skewed toward protumorigenic phenotypes, including the release of tumor-supportive cytokines and the expression of immunosuppressive molecules such as programmed cell death 1 ligand 1 (PD-L1). To understand the mechanism driving protumorigenic skewing in CLL, we evaluated the role of tumor cell-derived exosomes in the cross-talk with monocytes. We carried out RNA sequencing and proteome analyses of CLL-derived exosomes and identified noncoding Y RNA hY4 as a highly abundant RNA species that is enriched in exosomes from plasma of CLL patients compared with healthy donor samples...
July 28, 2017: Science Immunology
https://www.readbyqxmd.com/read/28754304/a-natural-ccr2-antagonist-relieves-tumor-associated-macrophage-mediated-immunosuppression-to-produce-a-therapeutic-effect-for-liver-cancer
#9
Wenbo Yao, Qian Ba, Xiaoguang Li, Huiliang Li, Shoude Zhang, Ya Yuan, Feng Wang, Xiaohua Duan, Jingquan Li, Weidong Zhang, Hui Wang
Hepatocellular carcinoma (HCC) is a common malignant tumor in the digestive tract with limited therapeutic choices. Although sorafenib, an orally administered multikinase inhibitor, has produced survival benefits for patients with advanced HCC, favorable clinical outcomes are limited due to individual differences and resistance. The application of immunotherapy, a promising approach for HCC is urgently needed. Macrophage infiltration, mediated by the CCL2/CCR2 axis, is a potential immunotherapeutic target. Here, we report that a natural product from Abies georgei, named 747 and related in structure to kaempferol, exhibits sensitivity and selectivity as a CCR2 antagonist...
August 2017: EBioMedicine
https://www.readbyqxmd.com/read/28747551/egfr-or-her2-inhibition-modulates-the-tumor-microenvironment-by-suppression-of-pd-l1-and-cytokines-release
#10
Koung Jin Suh, Ji Hea Sung, Jin Won Kim, Song-Hee Han, Hye Seung Lee, Ahrum Min, Mi Hyun Kang, Ji Eun Kim, Ji-Won Kim, Se Hyun Kim, Jeong-Ok Lee, Yu Jung Kim, Keun-Wook Lee, Jee Hyun Kim, Soo-Mee Bang, Seock-Ah Im, Jong Seok Lee
BACKGROUND: Characteristics of tumor microenvironment have been suggested as predictive markers of anti-EGFR or anti-HER2 treatment response. However, the effect of EGFR/HER2 signal blockade on the tumor immune microenvironment is unclear. METHODS: EGFR/HER2 pathway signaling and PD-L1 expression in gastric cancer cell lines were screened by western blot analysis. PD-L1 and HER2 expressions in 251 resected gastric tumors were determined by immunohistochemistry, and changes in EFGR, HER2, and PD-L1 expression in paired specimens between pre- and post-chemotherapy were evaluated...
July 12, 2017: Oncotarget
https://www.readbyqxmd.com/read/28744322/visualization-of-tumor-immune-interaction-target-specific-imaging-of-s100a8-a9-reveals-pre-metastatic-niche-establishment
#11
Michel Eisenblaetter, Fabian Flores-Borja, Jae Jin Lee, Christina Wefers, Hannah Smith, Rebekka Hueting, Margaret S Cooper, Philip J Blower, Dominic Patel, Manuel Rodriguez-Justo, Hanna Milewicz, Thomas Vogl, Johannes Roth, Andrew Tutt, Tobias Schaeffter, Tony Ng
Background Systemic cancer spread is preceded by the establishment of a permissive microenvironment in the target tissue of metastasis - the premetastatic niche. As crucial players in establishment of the pre-metastatic niche, myeloid derived suppressor cells (MDSC) release S100A8/A9, an exosomal protein that contributes to metastasis, angiogenesis, and immune suppression. We report the application of antibody-based single-photon emission computed tomography (SPECT) for detection of S100A8/A9 in vivo as an imaging marker for pre-metastatic tissue priming...
2017: Theranostics
https://www.readbyqxmd.com/read/28734227/continuous-delivery-of-neutralizing-antibodies-elevate-ccl2-levels-in-mice-bearing-mcf10ca1d-breast-tumor-xenografts
#12
Min Yao, Curtis Smart, Qingting Hu, Nikki Cheng
Chemokines are small soluble molecules that play critical roles in wound healing, infection, and cancer progression. In particular, overexpression of the C-C motif chemokine ligand 2 (CCL2) in multiple cancer types correlates with poor patient prognosis. Animal studies have shown that CCL2 signals to macrophages and breast cancer cells to promote tumor growth, invasion, and metastasis, indicating that CCL2 is a promising therapeutic target. However, the effectiveness of human-specific neutralizing antibodies has not been fully evaluated...
July 19, 2017: Translational Oncology
https://www.readbyqxmd.com/read/28730964/ccl2-is-modulated-by-cytokines-and-ppar-g-in-anaplastic-thyroid-cancer
#13
Silvia Martina Ferrari, Giusy Elia, Simona Piaggi, Enke Baldini, Salvatore Ulisse, Mario Miccoli, Gabriele Materazzi, Alessandro Antonelli, Poupak Fallahi
BACKGROUND AND OBJECTIVE: Chemokine (C-C motif) ligand (CCL)2, the prototype Th2 chemokine, is secreted by tumor cells, and has growth promoting effects. Whether CCL2 protumorigenic activities will be validated, then CCL2 and its receptor CCR2 may be therapeutic targets in cancer. METHODS: We tested in "primary human anaplastic thyroid carcinoma (ATC) cells" (ANA) versus "normal thyroid follicular cells" (TFC): a) CCL2 secretion basally, after IFN-g and/or TNF-a stimulation; b) PPARg activation by thiazolidinediones (TZDs), rosiglitazone or pioglitazone, on CCL2 secretion, and on proliferation and apoptosis in ANA...
July 19, 2017: Anti-cancer Agents in Medicinal Chemistry
https://www.readbyqxmd.com/read/28716525/peri-tumor-associated-fibroblasts-promote-intrahepatic-metastasis-of-hepatocellular-carcinoma-by-recruiting-cancer-stem-cells
#14
Jinghua Jiang, Fei Ye, Xue Yang, Chen Zong, Lu Gao, Yang Yang, Qiudong Zhao, Zhipeng Han, Lixin Wei
Fibroblasts have been reported to play an important role in hepatocellular carcinoma (HCC). However, the role of fibroblasts have not been fully understood. Conditioned medium collected from human peri-tumor tissue-derived fibroblasts (CM-pTAFs) showed high metastasis ability than human HCC tissues-derived fibroblasts (CM-TAFs). To determine what component was secreted from fibroblasts, we used Bio-Plex analysis system and compared the factors secreted from CM-pTAFs and CM-TAFs, found a series of up-regulated cytokines in the CM-pTAFs, including IL-6, CCL2, CXCL1, CXCL8, SCGF-β, HGF and VEGF...
September 28, 2017: Cancer Letters
https://www.readbyqxmd.com/read/28714025/effect-of-ccl2-sirna-on-proliferation-and-apoptosis-in-the-u251-human-glioma-cell-line
#15
Bin Lu, Yue Zhou, Zhongzhou Su, Ai Yan, Peng Ding
Glioma is one of the most common types of tumor of the central nervous system. Increased expression of C‑C motif chemokine 2 (CCL2) has previously been observed in various types of cancer. The effect of CCL2 small interfering (si)RNA on the proliferation, angiogenesis and apoptosis of the glioma cell line U251 was investigated in the present study. Data on CCL2 expression in glioma and normal tissues were obtained from The Cancer Genome Atlas. A total of 30 patients with glioma were enrolled in the present study...
September 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28710487/decreased-serum-apolipoprotein-a1-levels-are-associated-with-poor-survival-and-systemic-inflammatory-response-in-colorectal-cancer
#16
Päivi Sirniö, Juha P Väyrynen, Kai Klintrup, Jyrki Mäkelä, Markus J Mäkinen, Tuomo J Karttunen, Anne Tuomisto
Recent studies have reported of an association between high serum apolipoprotein A1 (APOA1) levels and favorable prognosis in several malignancies, while the significance of apolipoprotein B (APOB) in cancer is less well-known. In this study, we analyzed the correlation between serum APOA1 and APOB levels, and APOB/APOA1 ratio, and their associations with clinicopathologic parameters, the levels of twenty systemic inflammatory markers, and survival in 144 colorectal cancer (CRC) patients. We demonstrated that low serum APOA1 levels associated with advanced T-class and TNM-stage but low serum APOB levels did not significantly correlate with tumor characteristics...
July 14, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28683469/lurbinectedin-reduces-tumour-associated-macrophages-and-the-inflammatory-tumour-microenvironment-in-preclinical-models
#17
Cristina Belgiovine, Ezia Bello, Manuela Liguori, Ilaria Craparotta, Laura Mannarino, Lara Paracchini, Luca Beltrame, Sergio Marchini, Carlos M Galmarini, Alberto Mantovani, Roberta Frapolli, Paola Allavena, Maurizio D'Incalci
BACKGROUND: Lurbinectedin is a novel anticancer agent currently undergoing late-stage (Phase II /III) clinical evaluation in platinum-resistant ovarian, BRCA1/2-mutated breast and small-cell lung cancer. Lurbinectedin is structurally related to trabectedin and it inhibits active transcription and the DNA repair machinery in tumour cells. METHODS: In this study we investigated whether lurbinectedin has the ability to modulate the inflammatory microenvironment and the viability of myeloid cells in tumour-bearing mice...
July 6, 2017: British Journal of Cancer
https://www.readbyqxmd.com/read/28678759/danshen-improves-survival-of-patients-with-advanced-lung-cancer-and-targeting-the-relationship-between-macrophages-and-lung-cancer-cells
#18
Ching-Yuan Wu, Jong-Yuh Cherng, Yao-Hsu Yang, Chun-Liang Lin, Feng-Che Kuan, Yin-Yin Lin, Yu-Shih Lin, Li-Hsin Shu, Yu-Ching Cheng, Hung Te Liu, Ming-Chu Lu, Jthau Lung, Pau-Chung Chen, Hui Kuan Lin, Kuan-Der Lee, Ying-Huang Tsai
In traditional Chinese medicine, Salvia miltiorrhiza Bunge (danshen) is widely used in the treatment of numerous cancers. However, its clinical effort and mechanism in the treatment of advanced lung cancer are unclear. In our study, the in vivo protective effort of danshen in patients with advanced lung cancer were validated using data from the National Health Insurance Research Database in Taiwan. We observed in vitro that dihydroisotanshinone I (DT), a bioactive compound in danshen, exerts anticancer effects through many pathways...
June 28, 2017: Oncotarget
https://www.readbyqxmd.com/read/28662055/downregulation-of-adaptor-protein-myd88-compromises-the-angiogenic-potential-of-b16-murine-melanoma
#19
Lucas Daniel Trucco, Emiliano Roselli, Paula Araya, Nicolás Gonzalo Nuñez, Hebe Agustina Mena, José Luis Bocco, Soledad Negrotto, Mariana Maccioni
The mechanisms that link inflammatory responses to cancer development remain a subject of intense investigation, emphasizing the need to better understand the cellular and molecular pathways that create a tumor promoting microenvironment. The myeloid differentiation primary response protein MyD88 acts as a main adaptor molecule for the signaling cascades initiated from Toll-like receptors (TLRs) and the interleukin 1 receptor (IL-1R). MyD88 has been shown to contribute to tumorigenesis in many inflammation-associated cancer models...
2017: PloS One
https://www.readbyqxmd.com/read/28629469/a-putative-molecular-network-associated-with-colon-cancer-metastasis-constructed-from-microarray-data
#20
Songtao Chu, Haipeng Wang, Miao Yu
BACKGROUND: This study aimed to identify the potential molecular network associated with colon cancer metastasis. METHODS: A gene expression profile dataset (GSE40367) downloaded from Gene Expression Omnibus was used to identify and compare differentially expressed genes (DEGs) between primary colon adenocarcinoma tissues and matched tissue samples of liver metastases of colon adenocarcinoma. After the functional analysis of the DEGs, their protein-protein interactions (PPIs) were analyzed, and the transcription factors (TFs) and microRNAs (miRNAs) that regulated these DEGs were predicted...
June 19, 2017: World Journal of Surgical Oncology
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