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https://www.readbyqxmd.com/read/28852061/cd271-determines-migratory-properties-of-melanoma-cells
#1
Josefine Radke, Florian Roßner, Torben Redmer
Melanoma cell expression of the nerve growth factor receptor CD271 is associated with stem-like properties. However, the contributing role of the receptor in melanoma cell migration is elusive. Here, we explored extracranial (skin, soft tissue, lymph node and liver, n = 13) and matched brain metastases (BM, n = 12) and observed a heterogeneous distribution of phenotypically distinct subsets of CD271(+) cells. In addition, we observed that CD271 expression gradually rises along with melanoma progression and metastasis by exploration of publicly available expression data of nevi, primary melanoma (n = 31) and melanoma metastases (n = 54)...
August 29, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28842504/functional-defects-in-clostridium-difficile-tcdb-toxin-uptake-identify-cspg4-receptor-binding-determinants
#2
Pulkit Gupta, Zhifen Zhang, Seiji N Sugiman-Marangos, John Tam, Swetha Raman, Jean-Philippe Julien, Heather K Kroh, D Borden Lacy, Nicholas Murgolo, Kavitha Bekkari, Alex G Therien, Lorraine D Hernandez, Roman A Melnyk
Clostridium difficile is a major nosocomial pathogen that produces two exotoxins, TcdA and TcdB, with TcdB thought to be the primary determinant in human disease. TcdA and TcdB are large, multi-domain proteins, each harboring a cytotoxic glucosyltransferase domain that is delivered into the cytosol from endosomes via a translocation domain following receptor-mediated endocytosis of toxins from the cell surface. While there are currently no known host cell receptors for TcdA, three cell-surface receptors for TcdB have been identified: CSPG4, NECTIN3 and FZD1/2/7...
August 23, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28764769/anabolic-role-of-lysyl-oxidase-like-2-in-cartilage-of-knee-and-temporomandibular-joints-with-osteoarthritis
#3
Weam Alshenibr, Mustafa M Tashkandi, Saqer F Alsaqer, Yazeed Alkheriji, Amelia Wise, Sadanand Fulzele, Pushkar Mehra, Mary B Goldring, Louis C Gerstenfeld, Manish V Bais
BACKGROUND: Lysyl oxidase like-2 (LOXL2) is a copper-dependent amine oxidase. Our previous studies showed that LOXL2 is elevated during mouse fracture healing. The goal of this study was to evaluate the potential of LOXL2 to act as an anabolic agent in cartilage affected by osteoarthritis (OA). METHODS: LOXL2 was visualized in tissues from human knee and hip joints and temporomandibular joints (TMJ) by immunofluorescence. The activity of LOXL2 in human articular and TMJ chondrocytes was assessed by cell-based assays, microarray analysis, and RT-qPCR, and LOXL2-mediated activation of NF-κB and extracellular signal-related kinase (ERK) signaling pathways was measured by western blotting...
August 2, 2017: Arthritis Research & Therapy
https://www.readbyqxmd.com/read/28668095/cspg4-a-prototype-oncoantigen-for-translational-immunotherapy-studies
#4
REVIEW
Valeria Rolih, Giuseppina Barutello, Selina Iussich, Raffaella De Maria, Elena Quaglino, Paolo Buracco, Federica Cavallo, Federica Riccardo
Thanks to striking progress in both the understanding of anti-tumor immune response and the characterization of several tumor associated antigens (TAA), a more rational design and more sophisticated strategies for anti-tumor vaccination have been possible. However, the effectiveness of cancer vaccines in clinical trial is still partial, indicating that additional studies are needed to optimize their design and their pre-clinical testing. Indeed, anti-tumor vaccination success relies on the choice of the best TAA to be targeted and on the translational power of the pre-clinical model used to assess its efficacy...
July 1, 2017: Journal of Translational Medicine
https://www.readbyqxmd.com/read/28657611/cspg4-a-target-for-selective-delivery-of-human-cytolytic-fusion-proteins-and-trail
#5
REVIEW
Sandra Jordaan, Shivan Chetty, Neelakshi Mungra, Iris Koopmans, Peter E van Bommel, Wijnand Helfrich, Stefan Barth
Chondroitin-sulfate proteoglycan 4 (CSPG4) is a transmembrane glycoprotein overexpressed on malignant cells in several cancer types with only limited expression on normal cells. CSPG4 is implicated in several signaling pathways believed to drive cancer progression, particularly proliferation, motility and metastatic spread. Expression may serve as a prognostic marker for survival and risk of relapse in treatment-resistant malignancies including melanoma, triple negative breast cancer, rhabdomyosarcoma and acute lymphoblastic leukemia...
June 28, 2017: Biomedicines
https://www.readbyqxmd.com/read/28546458/proteoglycans-ion-channels-and-cell-matrix-adhesion
#6
REVIEW
Ioli Mitsou, Hinke A B Multhaupt, John R Couchman
Cell surface proteoglycans comprise a transmembrane or membrane-associated core protein to which one or more glycosaminoglycan chains are covalently attached. They are ubiquitous receptors on nearly all animal cell surfaces. In mammals, the cell surface proteoglycans include the six glypicans, CD44, NG2 (CSPG4), neuropilin-1 and four syndecans. A single syndecan is present in invertebrates such as nematodes and insects. Uniquely, syndecans are receptors for many classes of proteins that can bind to the heparan sulphate chains present on syndecan core proteins...
May 25, 2017: Biochemical Journal
https://www.readbyqxmd.com/read/28536635/the-regulatory-mechanisms-of-ng2-cspg4-expression
#7
REVIEW
Emmanuel Ampofo, Beate M Schmitt, Michael D Menger, Matthias W Laschke
Neuron-glial antigen 2 (NG2), also known as chondroitin sulphate proteoglycan 4 (CSPG4), is a surface type I transmembrane core proteoglycan that is crucially involved in cell survival, migration and angiogenesis. NG2 is frequently used as a marker for the identification and characterization of certain cell types, but little is known about the mechanisms regulating its expression. In this review, we provide evidence that the regulation of NG2 expression underlies inflammation and hypoxia and is mediated by methyltransferases, transcription factors, including Sp1, paired box (Pax) 3 and Egr-1, and the microRNA miR129-2...
2017: Cellular & Molecular Biology Letters
https://www.readbyqxmd.com/read/28445515/correlation-of-histopathologic-characteristics-to-protein-expression-and-function-in-malignant-melanoma
#8
Charlotte Welinder, Krzysztof Pawłowski, A Marcell Szasz, Maria Yakovleva, Yutaka Sugihara, Johan Malm, Göran Jönsson, Christian Ingvar, Lotta Lundgren, Bo Baldetorp, Håkan Olsson, Melinda Rezeli, Thomas Laurell, Elisabet Wieslander, György Marko-Varga
BACKGROUND: Metastatic melanoma is still one of the most prevalent skin cancers, which upon progression has neither a prognostic marker nor a specific and lasting treatment. Proteomic analysis is a versatile approach with high throughput data and results that can be used for characterizing tissue samples. However, such analysis is hampered by the complexity of the disease, heterogeneity of patients, tumors, and samples themselves. With the long term aim of quest for better diagnostics biomarkers, as well as predictive and prognostic markers, we focused on relating high resolution proteomics data to careful histopathological evaluation of the tumor samples and patient survival information...
2017: PloS One
https://www.readbyqxmd.com/read/28433626/thrombin-impairs-human-endometrial-endothelial-angiogenesis-implications-for-progestin-only-contraceptive-induced-abnormal-uterine-bleeding
#9
John P Shapiro, Ozlem Guzeloglu-Kayisli, Umit A Kayisli, Nihan Semerci, S Joseph Huang, Sefa Arlier, Kellie Larsen, Paolo Fadda, Frederick Schatz, Charles J Lockwood
OBJECTIVE: Progestin-only contraceptives induce abnormal uterine bleeding, accompanied by prothrombin leakage from dilated endometrial microvessels and increased thrombin generation by human endometrial stromal cell (HESC)-expressed tissue factor. Initial studies of the thrombin-treated HESC secretome identified elevated levels of cleaved chondroitin sulfate proteoglycan 4 (CSPG4), impairing pericyte-endothelial interactions. Thus, we investigated direct and CSPG4-mediated effects of thrombin in eliciting abnormal uterine bleeding by disrupting endometrial angiogenesis...
June 2017: Contraception
https://www.readbyqxmd.com/read/28287848/immunomodulating-and-immunoresistance-properties-of-cancer-initiating-cells-implications-for-the-clinical-success-of-immunotherapy
#10
REVIEW
Cristina Maccalli, Giorgio Parmiani, Soldano Ferrone
Cancer-initiating cells (CICs) represent a relatively rare subpopulation of cells endowed with self-renewal, stemness properties, tumorigenicity in immunodeficient mice, and resistance to standard therapies as well as to immunotherapy. Here, we review the biological and immunological characteristics of CICs with special focus on the immunomodulating mechanisms they utilize to escape from immunosurveillance. The recently developed immunotherapeutic strategies have yielded remarkable clinical results in many types of tumors, indicating that indeed a patient's immune system can mount an immune response, which is effective in controlling tumor growth...
April 2017: Immunological Investigations
https://www.readbyqxmd.com/read/28276839/visualization-of-vascular-mural-cells-in-developing-brain-using-genetically-labeled-transgenic-reporter-mice
#11
Bongnam Jung, Thomas D Arnold, Elisabeth Raschperger, Konstantin Gaengel, Christer Betsholtz
The establishment of a fully functional blood vascular system requires elaborate angiogenic and vascular maturation events in order to fulfill organ-specific anatomical and physiological needs. Although vascular mural cells, i.e. pericytes and vascular smooth muscle cells, are known to play fundamental roles during these processes, their characteristics during vascular development remain incompletely understood. In this report, we utilized transgenic reporter mice in which mural cells are genetically labeled to examine developing vascular mural cells in the central nervous system (CNS)...
January 1, 2017: Journal of Cerebral Blood Flow and Metabolism
https://www.readbyqxmd.com/read/28098860/chondroitin-sulfate-proteoglycan-protein-is-stimulated-by-interleukin%C3%A2-11-and-promotes-endometrial-epithelial-cancer-cell-proliferation-and-migration
#12
Amy Winship, Michelle Van Sinderen, Ariella Heffernan-Marks, Eva Dimitriadis
Endometrial cancer is the most common gynecological cancer. We identified interleukin 11 (IL11) as a critical mediator of endometrial tumourigenesis and demonstrated that IL11 regulates chondroitin sulfate proteoglycan (CSPG4) in human placental trophoblasts. CSPG4 is a cell membrane protein overexpressed in numerous human cancers, although its role in endometrial cancer has not been investigated. We examined CSPG4 expression and localization in primary human type I endometrioid grade (G) 1-3 tumours by qPCR and immunohistochemistry and determined whether IL11 stimulated CSPG4...
March 2017: International Journal of Oncology
https://www.readbyqxmd.com/read/28011196/isolating-subpopulations-of-human-epidermal-basal-cells-based-on-polyclonal-serum-against-trypsin-resistant-cspg4-epitopes
#13
Anders Patrik Gunnarsson, Rikke Christensen, Jeppe Praetorius, Uffe Birk Jensen
Chondroitin sulfate proteoglycan 4 (CSPG4) is highly expressed by human epidermal keratinocytes located at the tip of the dermal papilla where keratinocytes show characteristics of stem cells. However, since available antibodies to CSPG4 are directed against trypsin-sensitive epitopes we have been unable to study these keratinocytes isolated directly from skin samples by flow cytometry. By choosing epitopes of CSPG4 relatively close to the cell membrane we were able to generate a polyclonal antibody that successfully detects CSPG4 on keratinocytes after trypsinization...
January 15, 2017: Experimental Cell Research
https://www.readbyqxmd.com/read/27926479/decline-in-arylsulfatase-b-leads-to-increased-invasiveness-of-melanoma-cells
#14
Sumit Bhattacharyya, Leo Feferman, Kaoru Terai, Arkadiusz Z Dudek, Joanne K Tobacman
Arylsulfatase B (ARSB; N-acetylgalactosamine 4-sulfatase) is reduced in several malignancies, but levels in melanoma have not been investigated previously. Experiments were performed in melanoma cell lines to determine ARSB activity and impact on melanoma invasiveness. ARSB activity was reduced ~50% in melanoma cells compared to normal melanocytes. Silencing ARSB significantly increased the mRNA expression of chondroitin sulfate proteoglycan(CSPG)4 and pro-matrix metalloproteinase(MMP)-2, known mediators of melanoma progression...
January 17, 2017: Oncotarget
https://www.readbyqxmd.com/read/27879288/multi-omics-analysis-of-serum-samples-demonstrates-reprogramming-of-organ-functions-via-systemic-calcium-mobilization-and-platelet-activation-in-metastatic-melanoma
#15
Besnik Muqaku, Martin Eisinger, Samuel M Meier, Ammar Tahir, Tobias Pukrop, Sebastian Haferkamp, Astrid Slany, Albrecht Reichle, Christopher Gerner
Pathophysiologies of cancer-associated syndromes such as cachexia are poorly understood and no routine biomarkers have been established, yet. Using shotgun proteomics, known marker molecules including PMEL, CRP, SAA, and CSPG4 were found deregulated in patients with metastatic melanoma. Targeted analysis of 58 selected proteins with multiple reaction monitoring was applied for independent data verification. In three patients, two of which suffered from cachexia, a tissue damage signature was determined, consisting of nine proteins, PLTP, CD14, TIMP1, S10A8, S10A9, GP1BA, PTPRJ, CD44, and C4A, as well as increased levels of glycine and asparagine, and decreased levels of polyunsaturated phosphatidylcholine concentrations, as determined by targeted metabolomics...
January 2017: Molecular & Cellular Proteomics: MCP
https://www.readbyqxmd.com/read/27812322/tamoxifen-in-the-mouse-brain-implications-for-fate-mapping-studies-using-the-tamoxifen-inducible-cre-loxp-system
#16
Martin Valny, Pavel Honsa, Denisa Kirdajova, Zdenek Kamenik, Miroslava Anderova
The tamoxifen-inducible Cre-loxP system is widely used to overcome gene targeting pre-adult lethality, to modify a specific cell population at desired time-points, and to visualize and trace cells in fate-mapping studies. In this study we focused on tamoxifen degradation kinetics, because for all genetic fate-mapping studies, the period during which tamoxifen or its metabolites remain active in the CNS, is essential. Additionally, we aimed to define the tamoxifen administration scheme, enabling the maximal recombination rate together with minimal animal mortality...
2016: Frontiers in Cellular Neuroscience
https://www.readbyqxmd.com/read/27582000/roles-of-chondroitin-sulfate-proteoglycan-4-in-fibrogenic-adipogenic-differentiation-in-skeletal-muscle-tissues
#17
Shiho Takeuchi, Shin-Ichi Nakano, Katsuyuki Nakamura, Atsufumi Ozoe, Peggie Chien, Hidehito Yoshihara, Fumihiko Hakuno, Takashi Matsuwaki, Yasushi Saeki, Shin-Ichiro Takahashi, Keitaro Yamanouchi, Masugi Nishihara
Intramuscular adipose tissue and fibrous tissue are observed in some skeletal muscle pathologies such as Duchenne muscular dystrophy and sarcopenia, and affect muscle strength and myogenesis. They originate from common fibrogenic/adipogenic cells in the skeletal muscle. Thus, elucidating the regulatory mechanisms underlying fibrogenic/adipogenic cell differentiation is an important step toward the mediation of these disorders. Previously, we established a highly adipogenic progenitor clone, 2G11, from rat skeletal muscle and showed that basic fibroblast growth factor (bFGF) is pro-adipogenic in these cells...
October 1, 2016: Experimental Cell Research
https://www.readbyqxmd.com/read/27448975/photoimmunotheranostic-agents-for-triple-negative-breast-cancer-diagnosis-and-therapy-that-can-be-activated-on-demand
#18
Manal Amoury, Dirk Bauerschlag, Felix Zeppernick, Verena von Felbert, Nina Berges, Stefano Di Fiore, Isabell Mintert, Andreas Bleilevens, Nicolai Maass, Karen Bräutigam, Ivo Meinhold-Heerlein, Elmar Stickeler, Stefan Barth, Rainer Fischer, Ahmad Fawzi Hussain
Triple-negative breast cancer (TNBC) is a heterogeneous disease in which the tumors do not express estrogen receptor (ER), progesterone receptor (PgR) or human epidermal growth factor receptor 2 (HER2). Classical receptor-targeted therapies such as tamoxifen or trastuzumab are therefore unsuitable and combinations of surgery, chemotherapy and/or radiotherapy are required. Photoimmunotheranostics is a minimally invasive approach in which antibodies deliver nontoxic photosensitizers that emit light to facilitate diagnosis and produce cytotoxic reactive oxygen species to induce apoptosis and/or necrosis in cancer cells...
August 23, 2016: Oncotarget
https://www.readbyqxmd.com/read/27425618/mesenchymal-tumors-can-derive-from-ng2-cspg4-expressing-pericytes-with-%C3%AE-catenin-modulating-the-neoplastic-phenotype
#19
Shingo Sato, Yuning J Tang, Qingxia Wei, Makoto Hirata, Angela Weng, Ilkyu Han, Atsushi Okawa, Shu Takeda, Heather Whetstone, Puvindran Nadesan, David G Kirsch, Jay S Wunder, Benjamin A Alman
The cell of origin for most mesenchymal tumors is unclear. One cell type that contributes to this lineages is the pericyte, a cell expressing Ng2/Cspg4. Using lineage tracing, we demonstrated that bone and soft tissue sarcomas driven by the deletion of the Trp53 tumor suppressor, or desmoid tumors driven by a mutation in Apc, can derive from cells expressing Ng2/Cspg4. Deletion of the Trp53 tumor suppressor gene in these cells resulted in the bone and soft tissue sarcomas that closely resemble human sarcomas, while stabilizing β-catenin in this same cell type caused desmoid tumors...
July 26, 2016: Cell Reports
https://www.readbyqxmd.com/read/27340757/generation-of-reactive-astrocytes-from-ng2-cells-is-regulated-by-sonic-hedgehog
#20
Pavel Honsa, Martin Valny, Jan Kriska, Hana Matuskova, Lenka Harantova, Denisa Kirdajova, Lukas Valihrach, Peter Androvic, Mikael Kubista, Miroslava Anderova
NG2 cells, a fourth glial cell type in the adult mammalian central nervous system, produce oligodendrocytes in the healthy nervous tissue, and display wide differentiation potential under pathological conditions, where they could give rise to reactive astrocytes. The factors that control the differentiation of NG2 cells after focal cerebral ischemia (FCI) are largely unknown. Here, we used transgenic Cspg4-cre/Esr1/ROSA26Sortm14(CAG-tdTomato) mice, in which tamoxifen administration triggers the expression of red fluorescent protein (tomato) specifically in NG2 cells and cells derived therefrom...
September 2016: Glia
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