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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
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
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...
October 14, 2016: Breast: Official Journal of the European Society of Mastology
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
Pierre-Louis Loyher, Juliette Rochefort, Camille Baudesson de Chanville, Pauline Hamon, Géraldine Lescaille, Chloé Bertolus, Maude Guillot-Delost, Matthew Krummel, Francois M Lemoine, Christophe Combadière, Alexandre Boissonnas
The CCL2 chemokine receptor CCR2 drives cancer by mediating 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
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
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
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
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
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
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
Justyna Mikuła-Pietrasik, Paweł Uruski, Sebastian Szubert, Rafał Moszyński, Dariusz Szpurek, Stefan Sajdak, Andrzej Tykarski, Krzysztof Książek
Although undifferentiated tumors are the most lethal among all ovarian cancer histotypes, the exact reasons for this situation are unclear. This report was aimed at investigating whether the high aggressiveness of undifferentiated ovarian cancer may be associated with a biochemical composition of malignant ascites accumulating in the peritoneal cavity. We analyzed ascites from patients with undifferentiated, high-grade serous, endometrioid and clear-cell ovarian cancers, and from non-cancerous patients with respect to a group of soluble agents involved in cancer cell progression...
August 2016: Medical Oncology
Anne-Laure Chéné, Sènan d'Almeida, Thibaut Blondy, Julie Tabiasco, Sophie Deshayes, Jean-François Fonteneau, Laurent Cellerin, Yves Delneste, Marc Grégoire, Christophe Blanquart
INTRODUCTION: Mesothelioma is a rare and aggressive cancer related to asbestos exposure. We recently showed that pleural effusions (PEs) from patients with mesothelioma contain high levels of the C-C motif chemokine ligand 2 (CCL2) inflammatory chemokine. In the present work, we studied the effect of CCL2 contained in mesothelioma samples, particularly on monocyte recruitment. Then, we studied the fate of these monocytes in malignant pleural mesothelioma (MPM) PEs and their impact on tumor cells' properties...
October 2016: Journal of Thoracic Oncology
Zewei Wang, Huyang Xie, Lin Zhou, Zheng Liu, Hangcheng Fu, Yu Zhu, Le Xu, Jiejie Xu
PURPOSE: Chemokine (C-Cmotif) ligand 2 (CCL2) is a major chemokine that recruit monocytes and macrophages to the sites of inflammation. Recent researches have clarified that overexpression of CCL2 is associated with unfavorable prognosis in various cancer types. In this study, we aim to determine the prognostic value of CCL2 expression as well as its receptor C-C motif receptor type 2 (CCR2) in patients with non-metastatic clear cell renal cell carcinoma (ccRCC) after surgery. RESULTS: Both high CCL2 and CCR2 expression were remarkably correlated with shortened survival time (P < 0...
July 8, 2016: Oncotarget
Quan Huang, Haifeng Wei, Zhipeng Wu, Lin Li, Liangfang Yao, Zhengwang Sun, Lei Li, Zaijun Lin, Wei Xu, Shuai Han, Wenjiao Cao, Yunfei Xu, Dianwen Song, Xinghai Yang, Jianru Xiao
Lung cancer is the most common cause of cancer death worldwide. The poor survival rate is largely due to the extensive local invasion and metastasis. However, the mechanisms underlying the invasion and metastasis of lung cancer cells remain largely elusive. In this study, we examined the role of preferentially expressed antigen of melanoma (PRAME) in lung cancer metastasis. Our results show that PRAME is downregulated in lung adenocarcinoma and lung bone metastasis compared with normal human lung. Knockdown of PRAME decreases the expression of E-Cadherin and promotes the proliferation, invasion, and metastasis of lung cancer cells by regulating multiple critical genes, most of which are related to cell migration, including MMP1, CCL2, CTGF, and PLAU...
2016: PloS One
Rosa Mistica C Ignacio, Carla R Gibbs, Eun-Sook Lee, Deok-Soo Son
Obesity is characterized as an accumulation of adipose tissue mass represented by chronic, low-grade inflammation. Obesity-derived inflammation involves chemokines as important regulators contributing to the pathophysiology of obesity-related diseases such as cardiovascular disease, diabetes and some cancers. The obesity-driven chemokine network is poorly understood. Here, we identified the profiles of chemokine signature between human preadipocytes and adipocytes, using PCR arrays and qRT-PCR. Both preadipocytes and adipocytes showed absent or low levels in chemokine receptors in spite of some changes...
June 2016: Immune Network
Shinkyo Yoon, Byung Woog Kang, Su Yeon Park, Hye Jin Kim, Jun Seok Park, Gyu Seog Choi, Jong Gwang Kim
PURPOSE: Genetic polymorphisms in genes involved in the immune response are already known to affect the anti-tumor immune response. This study systematically investigated the association of 14 functional SNPs in a panel of 7 genes (CCL2, CCR2, NT5E, IDO1, LAG3, PDL1, and PDCD1) involved in immune response checkpoints with the survival outcomes of Korean patients with colorectal cancer (CRC). METHODS: The genomic DNA from 668 patients with curatively resected CRC was analyzed using a Sequenom MassARRAY, along with the association with recurrence-free survival (RFS) and overall survival (OS)...
August 2016: Journal of Cancer Research and Clinical Oncology
Jung-Hyun Kim, Sang-Su Kim, Ik-Hwan Han, Seobo Sim, Myoung-Hee Ahn, Jae-Sook Ryu
BACKGROUND: Chronic inflammation has a role in the pathogenesis of benign prostatic hyperplasia (BPH) and prostate cancer. Mast cells have been detected in chronic inflammatory infiltrate of the prostate, and it is possible that the interaction between prostate epithelial cells and Trichomonas vaginalis influences the activity of mast cells in the prostate stroma. Activated mast cells might influence the biological functions of nearby tissues and cells. In this study, we investigated whether mast cells reacted with the culture supernatant of BPH epithelial cells infected with T...
November 2016: Prostate
Cheng-Wei Li, Bor-Sen Chen
Recent studies have demonstrated that cell cycle plays a central role in development and carcinogenesis. Thus, the use of big databases and genome-wide high-throughput data to unravel the genetic and epigenetic mechanisms underlying cell cycle progression in stem cells and cancer cells is a matter of considerable interest. Real genetic-and-epigenetic cell cycle networks (GECNs) of embryonic stem cells (ESCs) and HeLa cancer cells were constructed by applying system modeling, system identification, and big database mining to genome-wide next-generation sequencing data...
June 13, 2016: Cell Cycle
Wei Bin Fang, Min Yao, Gage Brummer, Diana Acevedo, Nabil Alhakamy, Cory Berkland, Nikki Cheng
Triple negative breast cancers are an aggressive subtype of breast cancer, characterized by the lack of estrogen receptor, progesterone receptor and Her2 expression. Triple negative breast cancers are non-responsive to conventional anti-hormonal and Her2 targeted therapies, making it necessary to identify new molecular targets for therapy. The chemokine CCL2 is overexpressed in invasive breast cancers, and regulates breast cancer progression through multiple mechanisms. With few approaches to target CCL2 activity, its value as a therapeutic target is unclear...
June 7, 2016: Oncotarget
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