دورية أكاديمية
أعرض في EDS

IGF1R as a Key Target in High Risk, Metastatic Medulloblastoma.

التفاصيل البيبلوغرافية
العنوان: IGF1R as a Key Target in High Risk, Metastatic Medulloblastoma.
المؤلفون: Svalina MN; Children's Cancer Therapy Development Institute, Beaverton, OR USA., Kikuchi K; Department of Pediatrics, Oregon Health &Science University, Portland, OR 97239 USA., Abraham J; Department of Pediatrics, Oregon Health &Science University, Portland, OR 97239 USA., Lal S; Department of Pediatrics, Oregon Health &Science University, Portland, OR 97239 USA., Davare MA; Department of Pediatrics, Oregon Health &Science University, Portland, OR 97239 USA., Settelmeyer TP; Children's Cancer Therapy Development Institute, Beaverton, OR USA., Young MC; Children's Cancer Therapy Development Institute, Beaverton, OR USA., Peckham JL; Department of Pediatrics, Oregon Health &Science University, Portland, OR 97239 USA., Cho YJ; Department of Pediatrics, Oregon Health &Science University, Portland, OR 97239 USA.; Division of Child Neurology, Stanford Medicine Cancer Institute, Palo Alto, CA 94304 USA., Michalek JE; Department of Epidemiology and Biostatistics, University of Texas Health Science Center, San Antonio, TX 78229 USA., Hernandez BS; Department of Epidemiology and Biostatistics, University of Texas Health Science Center, San Antonio, TX 78229 USA., Berlow NE; Children's Cancer Therapy Development Institute, Beaverton, OR USA., Jackson M; Department of Pediatrics, Oregon Health &Science University, Portland, OR 97239 USA., Guillaume DJ; Division of Pediatric Neurosurgery, Department of Neurological Surgery, Oregon Health &Science University, Portland, OR 97239 USA., Selden NR; Division of Pediatric Neurosurgery, Department of Neurological Surgery, Oregon Health &Science University, Portland, OR 97239 USA., Bigner DD; Pediatric Brain Tumor Foundation Institute at Duke, Duke University Medical Center, Durham, NC 27705 USA., Nazemi KJ; Department of Pediatrics, Oregon Health &Science University, Portland, OR 97239 USA., Green SC; Department of Pathology, Oregon Health &Science University, Portland, OR 97239 USA., Corless CL; Department of Pathology, Oregon Health &Science University, Portland, OR 97239 USA., Gultekin S; Department of Pathology, Oregon Health &Science University, Portland, OR 97239 USA., Mansoor A; Department of Pathology, Oregon Health &Science University, Portland, OR 97239 USA., Rubin BP; Departments of Anatomic Pathology and Molecular Genetics, Taussig Cancer Center and Lerner Research Institute, Cleveland Clinic Foundation, Cleveland, OH 44195 USA., Woltjer R; Department of Pathology, Oregon Health &Science University, Portland, OR 97239 USA., Keller C; Children's Cancer Therapy Development Institute, Beaverton, OR USA.
المصدر: Scientific reports [Sci Rep] 2016 Jun 03; Vol. 6, pp. 27012. Date of Electronic Publication: 2016 Jun 03.
نوع المنشور: Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't
اللغة: English
بيانات الدورية: Publisher: Nature Publishing Group Country of Publication: England NLM ID: 101563288 Publication Model: Electronic Cited Medium: Internet ISSN: 2045-2322 (Electronic) Linking ISSN: 20452322 NLM ISO Abbreviation: Sci Rep Subsets: MEDLINE
أسماء مطبوعة: Original Publication: London : Nature Publishing Group, copyright 2011-
مواضيع طبية MeSH: Cerebellar Neoplasms/*cerebrospinal fluid , Medulloblastoma/*cerebrospinal fluid , Meningeal Neoplasms/*cerebrospinal fluid , Receptors, Somatomedin/*metabolism, Adolescent ; Antineoplastic Agents/pharmacology ; Biomarkers, Tumor/antagonists & inhibitors ; Biomarkers, Tumor/cerebrospinal fluid ; Biomarkers, Tumor/genetics ; Case-Control Studies ; Cell Adhesion ; Cell Line, Tumor ; Cell Movement ; Cell Proliferation ; Cerebellar Neoplasms/drug therapy ; Cerebellar Neoplasms/pathology ; Child ; Drug Screening Assays, Antitumor ; Female ; Gene Expression ; Humans ; Inhibitory Concentration 50 ; Insulin-Like Growth Factor Binding Protein 3/cerebrospinal fluid ; Insulin-Like Growth Factor Binding Protein 3/genetics ; Insulin-Like Growth Factor I/cerebrospinal fluid ; Insulin-Like Growth Factor I/genetics ; Male ; Matrix Metalloproteinase 9/cerebrospinal fluid ; Matrix Metalloproteinase 9/genetics ; Medulloblastoma/drug therapy ; Medulloblastoma/secondary ; Meningeal Neoplasms/drug therapy ; Meningeal Neoplasms/secondary ; Molecular Targeted Therapy ; Plasminogen Activator Inhibitor 1/cerebrospinal fluid ; Plasminogen Activator Inhibitor 1/genetics ; Receptor, IGF Type 1 ; Receptors, Somatomedin/antagonists & inhibitors ; Receptors, Somatomedin/genetics ; Tissue Inhibitor of Metalloproteinase-1/cerebrospinal fluid ; Tissue Inhibitor of Metalloproteinase-1/genetics
مستخلص: Risk or presence of metastasis in medulloblastoma causes substantial treatment-related morbidity and overall mortality. Through the comparison of cytokines and growth factors in the cerebrospinal fluid (CSF) of metastatic medulloblastoma patients with factors also in conditioned media of metastatic MYC amplified medulloblastoma or leptomeningeal cells, we were led to explore the bioactivity of IGF1 in medulloblastoma by elevated CSF levels of IGF1, IGF-sequestering IGFBP3, IGFBP3-cleaving proteases (MMP and tPA), and protease modulators (TIMP1 and PAI-1). IGF1 led not only to receptor phosphorylation but also accelerated migration/adhesion in MYC amplified medulloblastoma cells in the context of appropriate matrix or meningothelial cells. Clinical correlation suggests a peri-/sub-meningothelial source of IGF-liberating proteases that could facilitate leptomeningeal metastasis. In parallel, studies of key factors responsible for cell autonomous growth in MYC amplified medulloblastoma prioritized IGF1R inhibitors. Together, our studies identify IGF1R as a high value target for clinical trials in high risk medulloblastoma.
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معلومات مُعتمدة: P30 CA069533 United States CA NCI NIH HHS
المشرفين على المادة: 0 (Antineoplastic Agents)
0 (Biomarkers, Tumor)
0 (IGF1 protein, human)
0 (IGF1R protein, human)
0 (IGFBP3 protein, human)
0 (Insulin-Like Growth Factor Binding Protein 3)
0 (Plasminogen Activator Inhibitor 1)
0 (Receptors, Somatomedin)
0 (SERPINE1 protein, human)
0 (TIMP1 protein, human)
0 (Tissue Inhibitor of Metalloproteinase-1)
67763-96-6 (Insulin-Like Growth Factor I)
EC 2.7.10.1 (Receptor, IGF Type 1)
EC 3.4.24.35 (MMP9 protein, human)
EC 3.4.24.35 (Matrix Metalloproteinase 9)
تواريخ الأحداث: Date Created: 20160604 Date Completed: 20180416 Latest Revision: 20221109
رمز التحديث: 20231215
مُعرف محوري في PubMed: PMC4891740
DOI: 10.1038/srep27012
PMID: 27255663
قاعدة البيانات: MEDLINE
الوصف
تدمد:2045-2322
DOI:10.1038/srep27012