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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
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 pro-thrombin 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...
April 19, 2017: Contraception
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
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
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
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...
December 21, 2016: Experimental Cell Research
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
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
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
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
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
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
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
Nuor S M Jamil, Asim Azfer, Harrison Worrell, Donald M Salter
CSPG4/NG2 is a multifunctional transmembrane protein with limited distribution in adult tissues including articular cartilage. The purpose of this study was to investigate the possible roles of CSPG4/NG2 in chondrosarcomas and to establish whether this molecule may have potential for targeted therapy. Stable knock-down of CSPG4/NG2 in the JJ012 chondrosarcoma cell line by shRNA resulted in decreased cell proliferation and migration as well as a decrease in gene expression of the MMP (matrix metalloproteinase) 3 protease and ADAMTS4 (aggrecanase)...
April 2016: International Journal of Experimental Pathology
L A Piras, F Riccardo, S Iussich, L Maniscalco, F Gattino, M Martano, E Morello, S Lorda Mayayo, V Rolih, F Garavaglia, R De Maria, E Lardone, F Collivignarelli, D Mignacca, D Giacobino, S Ferrone, F Cavallo, P Buracco
Reported post-surgery 1-year survival rate for oral canine malignant melanoma (cMM) is around 30%; novel treatments are needed as the role of adjuvant chemotherapy is unclear. This prospective study regards adjuvant electrovaccination with human chondroitin sulfate proteoglycan-4 (hCSPG4)-encoded plasmid in 23 dogs with resected II/III-staged CSPG4-positive oral cMM compared with 19 dogs with resected only II/III-staged CSPG4-positive oral cMM. Vaccination resulted in 6-, 12-, 18- and 24-month survival rate of 95...
May 4, 2016: Veterinary and Comparative Oncology
Manal Amoury, Radoslav Mladenov, Thomas Nachreiner, Anh-Tuan Pham, Dmitrij Hristodorov, Stefano Di Fiore, Wijnand Helfrich, Alessa Pardo, Georg Fey, Michael Schwenkert, Theophilus Thepen, Fabian Kiessling, Ahmad F Hussain, Rainer Fischer, Katharina Kolberg, Stefan Barth
Chondroitin sulfate proteoglycan 4 (CSPG4) has been identified as a highly promising target antigen for immunotherapy of triple-negative breast cancer (TNBC). TNBC represents a highly aggressive heterogeneous group of tumors lacking expression of estrogen, progesterone and human epidermal growth factor receptor 2. TNBC is particularly prevalent among young premenopausal women. No suitable targeted therapies are currently available and therefore, novel agents for the targeted elimination of TNBC are urgently needed...
August 15, 2016: International Journal of Cancer. Journal International du Cancer
Andrew J Schoenfeld, Xinhui Wang, Yangyang Wang, Francis J Hornicek, G Petur Nielsen, Zhenfeng Duan, Soldano Ferrone, Joseph H Schwab
BACKGROUND: There are currently no generally accepted biomarkers used in the clinical treatment of chordoma tumors. CSPG4 has been associated with disease severity in other tumors. PURPOSE: This study aimed to characterize the frequency of CSPG4 expression in chordoma tumors and to correlate it with disease severity and clinical outcome. STUDY DESIGN: A retrospective review of clinical outcomes and immunohistochemical staining using tissue micro-array was carried out...
June 2016: Spine Journal: Official Journal of the North American Spine Society
J Ryu, C Lee
Selection signals of Korean cattle might be attributed largely to artificial selection for meat quality. Rapidly increased intragenic markers of newly annotated genes in the bovine genome would help overcome limited findings of genetic markers associated with meat quality at the selection signals in a previous study. The present study examined genetic associations of marbling score (MS) with intragenic nucleotide variants at selection signals of Korean cattle. A total of 39 092 nucleotide variants of 407 Korean cattle were utilized in the association analysis...
April 2016: Animal: An International Journal of Animal Bioscience
Katrin Spiesberger, Florian Paulfranz, Anton Egger, Judith Reiser, Claus Vogl, Judith Rudolf-Scholik, Corina Mayrhofer, Ludger Grosse-Hovest, Gottfried Brem
BACKGROUND: 30 years ago, the potential of bispecific antibodies to engage cytotoxic T cells for the lysis of cancer cells was discovered. Today a variety of bispecific antibodies against diverse cell surface structures have been developed, the majority of them produced in mammalian cell culture systems. Beside the r28M, described here, no such bispecific antibody is known to be expressed by transgenic livestock, although various biologicals for medical needs are already harvested-mostly from the milk-of these transgenics...
2015: PloS One
Ali Salanti, Thomas M Clausen, Mette Ø Agerbæk, Nader Al Nakouzi, Madeleine Dahlbäck, Htoo Z Oo, Sherry Lee, Tobias Gustavsson, Jamie R Rich, Bradley J Hedberg, Yang Mao, Line Barington, Marina A Pereira, Janine LoBello, Makoto Endo, Ladan Fazli, Jo Soden, Chris K Wang, Adam F Sander, Robert Dagil, Susan Thrane, Peter J Holst, Le Meng, Francesco Favero, Glen J Weiss, Morten A Nielsen, Jim Freeth, Torsten O Nielsen, Joseph Zaia, Nhan L Tran, Jeff Trent, John S Babcook, Thor G Theander, Poul H Sorensen, Mads Daugaard
Plasmodium falciparum engineer infected erythrocytes to present the malarial protein, VAR2CSA, which binds a distinct type chondroitin sulfate (CS) exclusively expressed in the placenta. Here, we show that the same CS modification is present on a high proportion of malignant cells and that it can be specifically targeted by recombinant VAR2CSA (rVAR2). In tumors, placental-like CS chains are linked to a limited repertoire of cancer-associated proteoglycans including CD44 and CSPG4. The rVAR2 protein localizes to tumors in vivo and rVAR2 fused to diphtheria toxin or conjugated to hemiasterlin compounds strongly inhibits in vivo tumor cell growth and metastasis...
October 12, 2015: Cancer Cell
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