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https://www.readbyqxmd.com/read/29776413/the-cxcr4-antagonist-plerixafor-amd3100-promotes-proliferation-of-ewing-sarcoma-cell-lines-in-vitro-and-activates-receptor-tyrosine-kinase-signaling
#1
Philipp Berning, Christiane Schaefer, Dagmar Clemens, Eberhard Korsching, Uta Dirksen, Jenny Potratz
BACKGROUND: The CXCR4 receptor antagonist plerixafor (AMD3100) is raising interest as an anti-cancer agent that disrupts the CXCL12-CXCR4 chemokine - receptor interaction between neoplastic cells and their microenvironment in tumor progression and metastasis. Here, we investigated plerixafor for anti-cancer activity in Ewing sarcoma, a rare and aggressive cancer of bone and soft tissues. METHODS: We used a variety of methods such as cell viability and migration assays, flow cytometry, phospho-tyrosine arrays and western blotting to determine plerixafor effects on five characterized Ewing sarcoma cell lines and a low-passage culture in vitro...
May 18, 2018: Cell Communication and Signaling: CCS
https://www.readbyqxmd.com/read/29769618/inhibitor-of-apoptosis-proteins-iaps-mediate-collagen-type-xi-alpha-1-driven-cisplatin-resistance-in-ovarian-cancer
#2
Miran Rada, Sameera Nallanthighal, Jennifer Cha, Kerry Ryan, Jessica Sage, Catherine Eldred, Maria Ullo, Sandra Orsulic, Dong-Joo Cheon
Although, cisplatin resistance is a major challenge in the treatment of ovarian cancer, the precise mechanisms underlying cisplatin resistance are not fully understood. Collagen type XI alpha 1 (COL11A1), a gene encoding a minor fibrillar collagen of the extracellular matrix, is identified as one of the most upregulated genes in cisplatin-resistant ovarian cancer and recurrent ovarian cancer. However, the exact functions of COL11A1 in cisplatin resistance are unknown. Here we demonstrate that COL11A1 binds to integrin α1β1 and discoidin domain receptor 2 (DDR2) and activates downstream signaling pathways to inhibit cisplatin-induced apoptosis in ovarian cancer cells...
May 17, 2018: Oncogene
https://www.readbyqxmd.com/read/29752300/intramyocardial-angiogenetic-stem-cells-and-epicardial-erythropoietin-save-the-acute-ischemic-heart
#3
Christian Klopsch, Anna Skorska, Marion Ludwig, Heiko Lemcke, Gabriela Maass, Ralf Gaebel, Martin Beyer, Cornelia Lux, Anita Toelk, Karina Müller, Christian Maschmeier, Sarah Rohde, Petra Mela, Brigitte Müller-Hilke, Stefan Jockenhoevel, Brigitte Vollmar, Robert Jaster, Robert David, Gustav Steinhoff
Ischemic heart failure still displays the highest mortality. An early boost of intracardiac regenerative key mechanisms and angiogenetic niche signaling in cardiac mesenchymal stem cells (MSCs) could improve myocardial infarction (MI) healing. Epicardial erythropoietin (EPO, 300U kg-1 ) was compared with intraperitoneal and intramyocardial EPO treatments after acute MI in rats (n=156). Real-time PCR and confocal microscopy revealed epicardial EPO treatment enhanced intracardiac regenerative key indicators (SDF-1, CXCR-4, CD34, Bcl-2, Cyclin D1, Cdc2, MMP2), induced TGF-β/WNT signaling in intramyocardial MSC niches through direct activation of AKT, upregulations of upstream signals FOS and Fzd7 and augmented intracardiac mesenchymal proliferation 24 hours after MI...
May 10, 2018: Disease Models & Mechanisms
https://www.readbyqxmd.com/read/29709482/spatial-localisation-of-discoidin-domain-receptor-2-ddr2-signalling-is-dependent-on-its-collagen-binding-and-kinase-activity
#4
Maciej T Luczynski, Peter T Harrison, Nadia Lima, Lukas Krasny, Angela Paul, Paul H Huang
Discoidin Domain Receptor 2 (DDR2) is a collagen-binding receptor tyrosine kinase that initiates delayed and sustained tyrosine phosphorylation signalling. To understand the molecular basis of this unique phosphorylation profile, here we utilise fluorescence microscopy to map the spatiotemporal localisation of DDR2 and tyrosine phosphorylated proteins upon stimulation with collagen. We show that cellular phosphorylated proteins are localised to the interface where DDR2 is in contact with collagen and not in the early endosomes or lysosomes...
April 27, 2018: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/29701112/multitasking-discoidin-domain-receptors-are-involved-in-several-and-specific-hallmarks-of-cancer
#5
Elodie Henriet, Margaux Sala, Aya Abou Hammoud, Adjanie Tuariihionoa, Julie Di Martino, Manon Ros, Frédéric Saltel
Discoidin domain receptors, DDR1 and DDR2, are two members of collagen receptor family that belong to tyrosine kinase receptor subgroup. Unlike other matrix receptor-like integrins, these collagen receptors have not been extensively studied. However, more and more studies are focusing on their involvement in cancer. These two receptors are present in several subcellular localizations such as intercellular junction or along type I collagen fibers. Consequently, they are involved in multiple cellular functions, for instance, cell cohesion, proliferation, adhesion, migration and invasion...
April 27, 2018: Cell Adhesion & Migration
https://www.readbyqxmd.com/read/29683819/primary-and-metastatic-melanoma-with-ntrk-fusions
#6
Cecilia Lezcano, Alexander N Shoushtari, Charlotte Ariyan, Travis J Hollmann, Klaus J Busam
A number of oncogenic driver mutations have been identified in melanocytic nevi and melanoma, but translocations also play a role in tumorigenesis and provide potential therapeutic targets for malignant lesions. Various translocations, such as those involving the anaplastic lymphoma kinase (ALK), neurotrophic tropomyosin receptor kinase 1 (NTRK1), and NTRK3 have been reported in spitzoid melanocytic neoplasms leading to kinase-fusion proteins that result in immunohistochemically detectable ALK or NTRK expression...
April 20, 2018: American Journal of Surgical Pathology
https://www.readbyqxmd.com/read/29652518/discoidin-domain-receptor-2-signaling-regulates-fibroblast-apoptosis-through-pdk1-akt
#7
Shijing Jia, Manisha Agarwal, Jibing Yang, Jeffrey C Horowitz, Eric S White, Kevin K Kim
Progressive fibrosis is a complication of many chronic diseases and collectively, organ fibrosis is the leading cause of death in the US. Fibrosis is characterized by accumulation of activated fibroblasts and excessive deposition of extracellular matrix proteins, especially type I collagen. Extensive research has supported a role for matrix signaling in propagating fibrosis but type I collagen itself is often considered an end product of fibrosis rather than an important regulator of continued collagen deposition...
April 13, 2018: American Journal of Respiratory Cell and Molecular Biology
https://www.readbyqxmd.com/read/29616590/ddr1-and-ddr2-physical-interaction-leads-to-signaling-interconnection-but-with-possible-distinct-functions
#8
Coralie Croissant, Adjanie Tuariihionoa, Marion Bacou, Wilfried Souleyreau, Margaux Sala, Elodie Henriet, Andreas Bikvalvi, Frederic Saltel, Patrick Auguste
Discoidin domain receptors 1 and 2 (DDR1 and DDR2) are members of the tyrosine kinase receptors activated after binding with collagen. DDRs are implicated in numerous physiological and pathological functions such as proliferation, adhesion and migration. Little is known about the expressions of the two receptors in normal and cancer cells and most of studies focus only on one receptor. Western blot analysis of DDR1 and DDR2 expression in different tumor cell lines shows an absence of high co-expression of the two receptors suggesting a deleterious effect of their presence at high amount...
April 4, 2018: Cell Adhesion & Migration
https://www.readbyqxmd.com/read/29455614/ddr1-a-major-player-in-renal-diseases
#9
Aude Dorison, Christos Chantziantoniou
Discoidin Domain Receptor 1 (DDR1) belongs to a family of two non-integrin collagen receptors, DDR1 and DDR2, which display a tyrosine kinase activity. DDR1 has been widely studied in different kind of pathologies including chronic kidney diseases (CKD). The aims of this commentary are 1. to review the existing information about DDR1 expression in healthy and diseased kidney, 2. to comment the data highlighting DDR1 as a major actor in CKD, 3. to suggest areas of research which require further investigation to better characterize the signaling pathways regulating DDR1 role in CKD...
February 27, 2018: Cell Adhesion & Migration
https://www.readbyqxmd.com/read/29382361/trypanosoma-cruzi-activates-mouse-cardiac-fibroblasts-in-vitro-leading-to-fibroblast-myofibroblast-transition-and-increase-in-expression-of-extracellular-matrix-proteins
#10
Laura Lacerda Coelho, Isabela Resende Pereira, Mirian Claudia de Souza Pereira, Liliane Mesquita, Joseli Lannes-Vieira, Daniel Adesse, Luciana Ribeiro Garzoni
BACKGROUND: Cardiac fibrosis is a consequence of chronic chagasic cardiomyopathy (CCC). In other cardiovascular diseases, the protagonist role of fibroblasts in cardiac fibrosis is well established. However, the role of cardiac fibroblasts (CFs) in fibrosis during the CCC is not clear. Here, our aim was to investigate the effect of Trypanosoma cruzi, the etiological agent of Chagas disease on CFs activation. METHODS: Cardiac fibroblasts were purified from primary cultures of mouse embryo cardiac cells...
January 30, 2018: Parasites & Vectors
https://www.readbyqxmd.com/read/29368620/molecular-profiling-of-lung-cancer-specimens-and-liquid-biopsies-using-maldi-tof-mass-spectrometry
#11
Eleonora Bonaparte, Chiara Pesenti, Laura Fontana, Rossella Falcone, Leda Paganini, Anna Marzorati, Stefano Ferrero, Mario Nosotti, Paolo Mendogni, Claudia Bareggi, Silvia Maria Sirchia, Silvia Tabano, Silvano Bosari, Monica Miozzo
BACKGROUND: Identification of predictive molecular alterations in lung adenocarcinoma is essential for accurate therapeutic decisions. Although several molecular approaches are available, a number of issues, including tumor heterogeneity, frequent material scarcity, and the large number of loci to be investigated, must be taken into account in selecting the most appropriate technique. MALDI-TOF mass spectrometry (MS), which allows multiplexed genotyping, has been adopted in routine diagnostics as a sensitive, reliable, fast, and cost-effective method...
January 12, 2018: Diagnostic Pathology
https://www.readbyqxmd.com/read/29367920/the-pronounced-high-expression-of-discoidin-domain-receptor-2-in-human-interstitial-lung-diseases
#12
Huan Bian, Xiaowei Nie, Xin Bu, Feng Tian, Libo Yao, Jingyu Chen, Jin Su
The most typical structural feature of human interstitial lung diseases (ILDs) is the accumulation of vast amounts of collagens within the lung interstitium. The membrane receptors that are responsible for recognising collagens and then transducing signals into the cells include four members of the integrin family (α1β1, α2β1, α10β1 and α11β1) and two members of the discoidin domain receptor family (DDR1 and DDR2). However, it remains unknown whether these six collagen receptors similarly contribute to the pathogenesis of fibrotic lung diseases...
January 2018: ERJ Open Research
https://www.readbyqxmd.com/read/29348456/twist1-induces-expression-of-discoidin-domain-receptor-2-to-promote-ovarian-cancer-metastasis
#13
Whitney R Grither, Laura M Divine, Eric H Meller, Daniel J Wilke, Riva A Desai, Andrew J Loza, Peinan Zhao, Anne Lohrey, Gregory D Longmore, Katherine C Fuh
The mesenchymal gene program has been shown to promote the metastatic progression of ovarian cancer; however, specific proteins induced by this program that lead to these metastatic behaviors have not been identified. Using patient derived tumor cells and established human ovarian tumor cell lines, we find that the Epithelial-to-Mesenchymal Transition inducing factor TWIST1 drives expression of discoidin domain receptor 2 (DDR2), a receptor tyrosine kinase (RTK) that recognizes fibrillar collagen as ligand...
March 2018: Oncogene
https://www.readbyqxmd.com/read/29330408/collagen-type-1-accelerates-healing-of-ruptured-fetal-membranes
#14
Haruta Mogami, Annavarapu Hari Kishore, R Ann Word
Preterm premature rupture of membranes (pPROM) is a major cause of preterm birth. Recently, extracellular matrix-directed treatment is applied for wound healing. Here, we used a pregnant mouse model to test the efficacy of collagen type 1 gel for healing of the prematurely ruptured fetal membranes. Although injection of PBS into the ruptured fetal membranes resulted in 40% closure, injection of collagen type 1 improved closure rates to 90% within 72 h. Macrophages of the M2 wound healing phenotype were entrapped in the collagen layer...
January 12, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29317515/intratumoural-heterogeneity-may-hinder-precision-medicine-strategies-in-patients-with-clear-cell-renal-cell-carcinoma
#15
Maria Rosaria Raspollini, Ilaria Montagnani, Rodolfo Montironi, Francesca Castiglione, Guido Martignoni, Liang Cheng, Antonio Lopez-Beltran
Clear cell renal cell carcinoma (ccRCC) is an heterogeneous tumour at architectural, cellular and molecular level, a reason why the 2014 International Society of Urological Pathology consensus recommended wide sampling of RCC masses to include at least 1 block/cm of tumour together with perpendicular sections of the tumour/perinephric fat interface and the tumour/renal sinus interface. Intratumoural molecular heterogeneity may be a limitation at the moment of defining precision medicine strategies based on gene mutation status...
January 9, 2018: Journal of Clinical Pathology
https://www.readbyqxmd.com/read/29302581/novel-genetic-associations-between-lung-cancer-and-indoor-radon-exposure
#16
Jung Ran Choi, Sang-Baek Koh, Seong Yong Park, Hye Run Kim, Hyojin Lee, Dae Ryong Kang
Background: Lung cancer is the leading cause of cancer-related death worldwide, for which smoking is considered as the primary risk factor. The present study was conducted to determine whether genetic alterations induced by radon exposure are associated with the susceptible risk of lung cancer in never smokers. Methods: To accurately identify mutations within individual tumors, next generation sequencing was conduct for 19 pairs of lung cancer tissue. The associations of germline and somatic variations with radon exposure were visualized using OncoPrint and heatmap graphs...
December 2017: Journal of Cancer Prevention
https://www.readbyqxmd.com/read/29250189/ddr2-facilitates-papillary-thyroid-carcinoma-epithelial-mesenchymal-transition-by-activating-erk2-snail1-pathway
#17
Zhong Liang, Wen-Jun Xie, Ming Zhao, Guo-Ping Cheng, Mei-Juan Wu
The upregulation of discoidin domain receptor tyrosine kinase 2 (DDR2) has been reported to be associated with poor prognosis and metastasis in numerous tumor types by inducing epithelial-mesenchymal transition (EMT); however, the expression profile of DDR2 in papillary thyroid carcinoma (PTC) with local metastasis and the effect of DDR2 on PTC cells remain unknown. The aim of the present study was to investigate the expression levels of DDR2 in tumor tissues of patients with PTC with local metastasis and cell lines and to determine the effect of DDR2 on EMT in PTC cells...
December 2017: Oncology Letters
https://www.readbyqxmd.com/read/29216386/an-exome-wide-association-study-identifies-new-susceptibility-loci-for-age-of-smoking-initiation-in-african-and-european-american-populations
#18
Keran Jiang, Zhongli Yang, Wenyan Cui, Kunkai Su, Jennie Z Ma, Thomas J Payne, Ming D Li
Introduction: Cigarette smoking is one of the largest causes of preventable death worldwide. This study aimed to identify susceptibility loci for age at smoking initiation (ASI) by performing exome-wide association analysis. Methods: A total of 2,510 smokers of either African-American (AA) or European-American (EA) origin were genotyped and analyzed at both the single nucleotide polymorphism (SNP) and gene levels. After removal of those SNPs with minor allele frequency (<0...
December 5, 2017: Nicotine & Tobacco Research: Official Journal of the Society for Research on Nicotine and Tobacco
https://www.readbyqxmd.com/read/29205098/platelet-derived-growth-factor-receptor-alpha-expressing-cardiac-progenitor-cells-can-be-derived-from-previously-cryopreserved-human-heart-samples
#19
Thi Y L Le, Hilda A Pickett, Cristobal G Dos Remedios, Pasquale M Barbaro, Eddy Kizana, James J H Chong
Cardiac progenitor cells (CPCs) are being developed as a promising treatment for heart failure. Although clinical trials have predominantly used donor cardiac biopsies to derive CPCs, a better solution could be to use previously cryopreserved human heart tissue. This would enable timely and convenient access to healthy and young heart samples for CPC production. However, few studies have attempted to isolate CPCs from previously cryopreserved heart tissue. In this study, we isolated CPCs from eight nondiseased human heart samples previously cryopreserved as part of the Sydney Heart Bank...
February 1, 2018: Stem Cells and Development
https://www.readbyqxmd.com/read/29199670/targeted-therapy-in-nonsmall-cell-lung-cancer
#20
REVIEW
T Puri
Activating mutations in the epidermal growth factor receptor gene and rearrangement of the anaplastic lymphoma kinase gene exemplify the molecular characterization of nonsmall cell lung cancer (NSCLC), particularly adenocarcinoma, and its therapeutic relevance. Several genetic alterations with prognostic and predictive role, including ROS, RET, MET, KRAS, have now been identified in adenocarcinoma and some such as DDR2 and fibroblast growth factor receptor 1 in squamous cell carcinoma. This has heralded the development of agents targeted against these aberrations...
January 2017: Indian Journal of Cancer
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