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https://www.readbyqxmd.com/read/28103615/radiation-induced-lung-metastasis-development-is-mt1-mmp-dependent-in-a-triple-negative-breast-cancer-mouse-model
#1
Gina Bouchard, Hélène Therriault, Sameh Geha, Rachel Bujold, Caroline Saucier, Benoit Paquette
BACKGROUND: The prognosis of triple-negative breast cancer (TNBC) is still difficult to establish. Some TNBC benefit from radiotherapy (RT) and are cured, while in other patients metastases appear during the first 3 years after treatment. In this study, an animal model of TNBC was used to determine whether the expression of the cell membrane protease MT1-MMP in cancer cells was associated with radiation-stimulated development of lung metastases. METHODS: Using invasion chambers, irradiated fibroblasts were used as chemoattractants to assess the invasiveness of TNBC D2A1 cell lines showing downregulated expression of MT1-MMP, which were compared with D2A1-wt (wild-type) and D2A1 shMT1-mock (empty vector) cell lines...
January 19, 2017: British Journal of Cancer
https://www.readbyqxmd.com/read/28103135/reconstitution-of-a-metastatic-resistant-tumor-microenvironment-with-cancer-associated-fibroblasts-enables-metastasis
#2
Takuya Murata, Eisuke Mekada, Robert M Hoffman
The tumor microenvironment is critical for metastasis to occur. Subcutaneous xenografts of tumors in immunodeficient mice are usually encapsulated and rarely metastasize as opposed to orthotopic tumors which metastasize if the original tumor was metastatic. In the present report, we were able to reconstitute a metastatic tumor microenvironment by subcutaneously co-transplanting a human cervical cancer cell line and human cervical cancer-associated fibroblasts (CAFs), in athymic mice, which resulted in lymph node metastasis in 40% of the animals...
January 19, 2017: Cell Cycle
https://www.readbyqxmd.com/read/28102840/cancer-associated-fibroblasts-enact-field-cancerization-by-promoting-extratumoral-oxidative-stress
#3
Jeremy Soon Kiat Chan, Ming Jie Tan, Ming Keat Sng, Ziqiang Teo, Terri Phua, Chee Chong Choo, Liang Li, Pengcheng Zhu, Nguan Soon Tan
Histological inspection of visually normal tissue adjacent to neoplastic lesions often reveals multiple foci of cellular abnormalities. This suggests the presence of a regional carcinogenic signal that spreads oncogenic transformation and field cancerization. We observed an abundance of mutagenic reactive oxygen species in the stroma of cryosectioned patient tumor biopsies, indicative of extratumoral oxidative stress. Diffusible hydrogen peroxide (H2O2) was elevated in the conditioned medium of cultured skin epithelia at various stages of oncogenic transformation, and H2O2 production increased with greater tumor-forming and metastatic capacity of the studied cell lines...
January 19, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/28101903/development-and-characterization-of-anti-glycopeptide-monoclonal-antibodies-against-human-podoplanin-using-glycan-deficient-cell-lines-generated-by-crispr-cas9-and-talen
#4
Mika K Kaneko, Takuro Nakamura, Ryusuke Honma, Satoshi Ogasawara, Yuki Fujii, Shinji Abe, Michiaki Takagi, Hiroyuki Harada, Hiroyoshi Suzuki, Yasuhiko Nishioka, Yukinari Kato
Human podoplanin (hPDPN), which binds to C-type lectin-like receptor-2 (CLEC-2), is involved in platelet aggregation and cancer metastasis. The expression of hPDPN in cancer cells or cancer-associated fibroblasts indicates poor prognosis. Human lymphatic endothelial cells, lung-type I alveolar cells, and renal glomerular epithelial cells express hPDPN. Although numerous monoclonal antibodies (mAbs) against hPDPN are available, they recognize peptide epitopes of hPDPN. Here, we generated a novel anti-hPDPN mAb, LpMab-21...
January 19, 2017: Cancer Medicine
https://www.readbyqxmd.com/read/28099917/cleavage-of-fibulin-2-by-the-aggrecanases-adamts-4-and-adamts-5-contributes-to-the-tumorigenic-potential-of-breast-cancer-cells
#5
Tania Fontanil, Saúl Álvarez-Teijeiro, M Ángeles Villaronga, Yamina Mohamedi, Laura Solares, Angela Moncada-Pazos, José A Vega, Olivia García-Suárez, Marcos Pérez-Basterrechea, Juana M García-Pedrero, Alvaro J Obaya, Santiago Cal
Fibulin-2 participates in the assembly of extracellular matrix components through interactions with multiple ligands and promotes contacts between cells and their surrounding environment. Consequently, identification of processes that could lead to an altered Fibulin-2 could have a major impact not only in the maintenance of tissue architecture and morphogenesis but also in pathological situations including cancer. Herein, we have investigated the ability of the secreted metalloproteases ADAMTS-4 and ADAMTS-5 to digest Fibulin-2...
January 13, 2017: Oncotarget
https://www.readbyqxmd.com/read/28099150/elimination-of-quiescent-slow-cycling-cells-via-reducing-quiescence-depth-by-natural-compounds-purified-from-ganoderma-lucidum
#6
Jian Dai, Matthew A Miller, Nicholas J Everetts, Xia Wang, Peng Li, Ye Li, Jian-Hua Xu, Guang Yao
The medical mushroom Ganoderma lucidum has long been used in traditional Chinese medicine and shown effective in the treatment of many diseases including cancer. Here we studied the cytotoxic effects of two natural compounds purified from Ganoderma lucidum, ergosterol peroxide and ganodermanondiol. We found that these two compounds exhibited cytotoxicity not only against fast proliferating cells, but on quiescent, slow-cycling cells. Using a fibroblast cell-quiescence model, we found that the cytotoxicity on quiescent cells was due to induced apoptosis, and was associated with a shallower quiescent state in compound-treated cells, resultant from the increased basal activity of an Rb-E2F bistable switch that controls quiescence exit...
January 13, 2017: Oncotarget
https://www.readbyqxmd.com/read/28098859/dna-damage-response-defect-in-williams-beuren-syndrome
#7
David Guenat, Giuseppe Merla, Eric Deconinck, Christophe Borg, Pierre-Simon Rohrlich
Williams-Beuren syndrome (WBS, no. OMIM 194050) is a rare multisystem genetic disorder caused by a microdeletion on chromosome 7q11.23 and characterized by cardiovascular malformations, mental retardation, and a specific facial dysmorphism. Recently, we reported that a series of non‑Hodgkin's lymphoma occurs in children with WBS and thus hypothesized that a predisposition to cancer may be associated with this genetic disorder. The aim of the present study was to ascertain the role played by three genes hemizygously deleted in WBS (RFC2, GTF2I and BAZ1B) in DNA damage response pathways...
January 17, 2017: International Journal of Molecular Medicine
https://www.readbyqxmd.com/read/28097809/cancer-associated-fibroblasts-promote-m2-polarization-of-macrophages-in-pancreatic-ductal-adenocarcinoma
#8
Aibin Zhang, Yigang Qian, Zhou Ye, Haiyong Chen, Haiyang Xie, Lin Zhou, Yan Shen, Shusen Zheng
Pancreatic ductal adenocarcinoma (PDAC) is characterized by remarkable desmoplasia with infiltration of distinct cellular components. Cancer-associated fibroblasts (CAFs) has been shown to be among the most prominent cells and played a significant role in shaping the tumor microenvironment by interacting with other type of cells. Here, we aimed to investigate the effect of CAFs in modulating phenotype of tumor-associated macrophages (TAM). Under treatment of CAFs conditioned medium (CM) or direct co-culture with CAFs, monocytes exhibited enhanced expression of CD206 and CD163 compared with control group (P < 0...
January 18, 2017: Cancer Medicine
https://www.readbyqxmd.com/read/28097375/hypoxia-induced-fibroblast-growth-factor-11-stimulates-osteoclast-mediated-resorption-of-bone
#9
Helen J Knowles
Over-activation of osteoclasts is directly responsible for pathological bone loss in conditions such as rheumatoid arthritis and cancer metastasis to bone. Hypoxia is a common feature of these conditions, associated with poor prognosis, which also stimulates osteoclast-mediated bone resorption via induction of the hypoxia-inducible transcription factor HIF-1α. Here, we investigate the effects of fibroblast growth factor 11 (FGF11) on osteoclast function. FGF11 is an intracellular FGF that was induced both by hypoxia (2% O2, p < 0...
January 18, 2017: Calcified Tissue International
https://www.readbyqxmd.com/read/28088809/fibroblast-growth-factor-receptor-1-fgfr1-partly-related-to-vascular-endothelial-growth-factor-receptor-2-vegfr2-and-microvessel-density-is-an-independent-prognostic-factor-for-non-small-cell-lung-cancer
#10
Dan Pu, Jiewei Liu, Zhixi Li, Jiang Zhu, Mei Hou
BACKGROUND This study aimed to explore the correlation between FGFR1 and clinical features, including survival analysis and the promotion of angiogenesis by fibroblast growth factor receptor 1 (FGFR1) and vascular endothelial growth factor receptor 2 (VEGFR2). FGFR1 gene amplification has been found in non-small cell lung cancer (NSCLC). However, the prognostic value of FGFR1 and the correlation between FGFR1 and clinical features are still controversial. MATERIAL AND METHODS A total of 92 patients with NSCLC who underwent R0 resection between July 2006 and July 2008 were enrolled in the study...
January 15, 2017: Medical Science Monitor: International Medical Journal of Experimental and Clinical Research
https://www.readbyqxmd.com/read/28088105/tectona-grandis-leaf-extract-free-and-associated-with-nanoemulsions-as-a-possible-photosensitizer-of-mouse-melanoma-b16-cell
#11
Cydia de Menezes Furtado, Fernando Sergio Escocio Drumond Viana de Faria, Ricardo Bentes Azevedo, Karen Py-Daniel, Ana Lygia Dos Santos Camara, Jaqueline Rodriguez da Silva, Everton de Holanda Oliveira, Anselmo Fortunato Ruiz Rodriguez, Igor Anatolievich Degterev
Over the past six years we have been studying extracts from tropical, specially Amazon, plants, to search for new sensitizers for photodynamic therapy of cancer and infectious diseases. Tectona grandis is a genus of tropical hardwood trees in the mint family, Lamiaceae. That is native to south and southeast Asia, but since the end of the 20th century is also gaining ground in the Amazon. The present work aims to evaluate the photodynamic potential of hydro-alcoholic extract from Tectona grandis LF leaves (TGE) and the same extract prepared as the oil-water nanoemulsion (TGE-NE) against melanoma B16 F10 cells...
January 5, 2017: Journal of Photochemistry and Photobiology. B, Biology
https://www.readbyqxmd.com/read/28087599/long-non-coding-rna-linc00092-acts-in-cancer-associated-fibroblasts-to-drive-glycolysis-and-progression-of-ovarian-cancer
#12
Linjie Zhao, Gaili Ji, Xiaobing Le, Chenlu Wang, Lian Xu, Min Feng, Yaguang Zhang, Huiliang Yang, Yu Xuan, Yanfei Yang, Lingzi Lei, Qilian Yang, Wayne Bond Lau, Bonnie Lau, Yi Chen, Xiangbing Deng, Shaohua Yao, Tao Yi, Xia Zhao, Yuquan Wei, Shengtao Zhou
The majority of patients with epithelial ovarian cancer are diagnosed at a late stage when peritoneal metastases exist, however, there is little knowledge of the metastatic process in this disease setting. In this study, we report the identification of the long non-coding RNA LINC00092 as a nodal driver of metastatic progression mediated by cancer-associated fibroblasts (CAF). Pro-metastatic properties of CAF in vitro and in vivo were found to associate with elevated expression of the chemokine CXCL14. In clinical specimens, elevated levels of CXCL14 in CAF also correlated with poor prognosis...
January 13, 2017: Cancer Research
https://www.readbyqxmd.com/read/28087332/exo-mfa-a-13c-metabolic-flux-analysis-to-dissect-tumor-microenvironment-secreted-exosome-contributions-towards-cancer-cell-metabolism
#13
Abhinav Achreja, Hongyun Zhao, Lifeng Yang, Tae Hyun Yun, Juan Marini, Deepak Nagrath
Dissecting the pleiotropic roles of tumor micro-environment (TME) on cancer progression has been brought to the foreground of research on cancer pathology. Extracellular vesicles such as exosomes, transport proteins, lipids, and nucleic acids, to mediate intercellular communication between TME components and have emerged as candidates for anti-cancer therapy. We previously reported that cancer-associated fibroblast (CAF) derived exosomes (CDEs) contain metabolites in their cargo that are utilized by cancer cells for central carbon metabolism and promote cancer growth...
January 10, 2017: Metabolic Engineering
https://www.readbyqxmd.com/read/28077438/fibroblast-drug-scavenging-increases-intratumoural-gemcitabine-accumulation-in-murine-pancreas-cancer
#14
E Hessmann, M S Patzak, L Klein, N Chen, V Kari, I Ramu, T E Bapiro, K K Frese, A Gopinathan, F M Richards, D I Jodrell, C Verbeke, X Li, R Heuchel, J M Löhr, S A Johnsen, T M Gress, V Ellenrieder, A Neesse
OBJECTIVE: Desmoplasia and hypovascularity are thought to impede drug delivery in pancreatic ductal adenocarcinoma (PDAC). However, stromal depletion approaches have failed to show clinical responses in patients. Here, we aimed to revisit the role of the tumour microenvironment as a physical barrier for gemcitabine delivery. DESIGN: Gemcitabine metabolites were analysed in LSL-Kras(G12D/+); LSL-Trp53(R172H/+); Pdx-1-Cre (KPC) murine tumours and matched liver metastases, primary tumour cell lines, cancer-associated fibroblasts (CAFs) and pancreatic stellate cells (PSCs) by liquid chromatography-mass spectrometry/mass spectrometry...
January 10, 2017: Gut
https://www.readbyqxmd.com/read/28077301/mir-124-down-regulation-is-critical-for-cancer-associated-fibroblasts-enhanced-tumor-growth-of-oral-carcinoma
#15
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/28072738/expression-quantitative-trait-loci-for-pi3k-akt-pathway
#16
Dongchan Ryu, Chaeyoung Lee
A genome-wide association study (GWAS) was conducted to identify expression quantitative trait loci (eQTLs) for the genes involved in phosphatidylinositol-3-kinase/v-akt murine thymoma viral oncogene homolog (PI3K/AKT) pathway.Data on mRNA expression of 341 genes in lymphoblastoid cell lines of 373 Europeans recruited by the 1000 Genomes Project using Illumina HiSeq2000 were utilized. We used their genotypes at 5,941,815 nucleotide variants obtained by Genome Analyzer II and SOLiD.The association analysis revealed 4166 nucleotide variants associated with expression of 85 genes (P < 5 × 10)...
January 2017: Medicine (Baltimore)
https://www.readbyqxmd.com/read/28069875/15%C3%A2-methoxypuupehenol-induces-antitumor-effects-in-vitro-and-in-vivo-against-human-glioblastoma-and-breast-cancer-models
#17
Tyvette Hilliard, Gabriella Miklossy, Christopher Chock, Peibin Yue, Philip Williams, James Turkson
Studies with 15∝-methoxypuupehenol (15∝-MP), obtained from the extracts of Hyrtios sp., identified putative targets that are associated with its antitumor effects against human glioblastoma (GBM) and breast cancer. In the human GBM (U251MG) or breast cancer (MDA-MB-231) cells, treatment with 15∝-MP repressed pY705Stat3 (Signal Transducer and Activator of Transcription 3), pErk1/2 (extracellular signal-regulated kinase), pS147CyclinB1, pY507Alk (Anaplastic lymphoma kinase), and pY478ezrin levels, and induced pS10merlin, without inhibiting pJAK2 (Janus kinase) or pAkt induction...
January 9, 2017: Molecular Cancer Therapeutics
https://www.readbyqxmd.com/read/28068323/the-nogo-b-receptor-promotes-ras-plasma-membrane-localization-and-activation
#18
B Zhao, W Hu, S Kumar, P Gonyo, U Rana, Z Liu, B Wang, W Q Duong, Z Yang, C L Williams, Q R Miao
The localization of prenylated Ras at the plasma membrane promotes activation of Ras by receptor tyrosine kinases and stimulates oncogenic signaling by mutant Ras. The Nogo-B receptor (NgBR) is a transmembrane receptor that contains a conserved hydrophobic pocket. Here, we demonstrate that the NgBR promotes the membrane accumulation of Ras by directly binding prenylated Ras at the plasma membrane. We show that NgBR knockdown diminishes the membrane localization of Ras in multiple cell types. NgBR overexpression in NIH-3T3 fibroblasts increases membrane-associated Ras, induces the transformed phenotype in vitro, and promotes the formation of fibrosarcoma in nude mice...
January 9, 2017: Oncogene
https://www.readbyqxmd.com/read/28060811/stromal-fibroblasts-from-the-interface-zone-of-triple-negative-breast-carcinomas-induced-epithelial-mesenchymal-transition-and-its-inhibition-by-emodin
#19
Hsiang-Chi Hsu, Liang-Chih Liu, Hao-Yu Wang, Chao-Ming Hung, Ying-Chao Lin, Chi-Tang Ho, Tzong-Der Way
"Triple negative breast cancer" (TNBC) is associated with a higher rate and earlier time of recurrence and worse prognosis after recurrence. In this study, we aimed to examine the crosstalk between fibroblasts and TNBC cells. The fibroblasts were isolated from TNBC patients' tissue in tumor burden zones, distal normal zones and interface zones. The fibroblasts were indicated as cancer-associated fibroblasts (CAFs), normal zone fibroblasts (NFs) and interface zone fibroblasts (INFs). Our study found that INFs grew significantly faster than NFs and CAFs in vitro...
2017: PloS One
https://www.readbyqxmd.com/read/28056982/different-clinical-significance-of-fgfr1-4-expression-between-diffuse-type-and-intestinal-type-gastric-cancer
#20
Mikito Inokuchi, Hideaki Murase, Sho Otsuki, Tatsuyuki Kawano, Kazuyuki Kojima
BACKGROUND: Receptor tyrosine kinases promote tumor progression in many cancers, although oncologic activation differs between diffuse-type gastric cancer (DGC) and intestinal-type gastric cancer (IGC). Fibroblast growth factor receptor (FGFR) is one RTK, and we previously reported the clinical significance of FGFR1, 2, 3, and 4 in gastric cancer. The aim of the present study was to reevaluate the clinical significance of FGFR1-4 expression separately in DGC and IGC. METHODS: Tumor samples, including 109 DGCs and 100 IGCs, were obtained from patients who underwent gastrectomy between 2003 and 2007 in our institution...
January 5, 2017: World Journal of Surgical Oncology
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