Neuronal differentiation of synovial sarcoma and its therapeutic application.

Abstract	Synovial sarcoma is a rare sarcoma of unknown histologic origin. We previously reported the gene expression profile of synovial sarcoma was closely related to that of malignant peripheral nerve sheath tumors, and the fibroblast growth factor (FGF) signal was one of the main growth signals in synovial sarcoma. Here we further demonstrate the neural origin of synovial sarcoma using primary tumors and cell lines. The expression of neural tissue-related genes was confirmed in synovial sarcoma tumor tissues, but the expression of some genes was absent in synovial sarcoma cell lines. Treatment of synovial sarcoma cell lines with BMP4 or FGF2 enhanced or restored the expression of neural tissue-related genes and induced a neuron-like morphology with positive Tuj-1 expression. Treatment with all-trans-retinoic acid also induced the expression of neural tissue-related genes in association with growth inhibition, which was not observed in other cell lines except a malignant peripheral nerve sheath tumor cell line. A growth-inhibitory effect of all-trans-retinoic acid was also observed for xenografted tumors in athymic mice. The simultaneous treatment with FGF signal inhibitors enhanced the growth-inhibitory effect of all-trans-retinoic acid, suggesting the combination of growth signaling inhibition and differentiation induction could be a potential molecular target for treating synovial sarcoma.
Authors	Tatsuya Ishibe, Tomitaka Nakayama, Tomoki Aoyama, Takashi Nakamura, Junya Toguchida
Journal	Clinical orthopaedics and related research (Clin Orthop Relat Res) Vol. 466 Issue 9 Pg. 2147-55 (Sep 2008) ISSN: 1528-1132 [Electronic] United States
PMID	18563503 (Publication Type: Journal Article, Review)
Chemical References	Antineoplastic Agents Ascl1 protein, mouse BMP4 protein, human Basic Helix-Loop-Helix Transcription Factors Bmp4 protein, mouse Bone Morphogenetic Protein 4 Bone Morphogenetic Proteins Hes1 protein, mouse Homeodomain Proteins Intermediate Filament Proteins NES protein, human Nerve Growth Factors Nerve Tissue Proteins Nes protein, mouse Nestin Receptor, Nerve Growth Factor Receptors, Retinoic Acid Recombinant Proteins S100 Calcium Binding Protein beta Subunit S100 Proteins Transcription Factor HES-1 retinoic acid binding protein I, cellular Fibroblast Growth Factor 2 Tretinoin
Topics	Animals Antineoplastic Agents (pharmacology) Basic Helix-Loop-Helix Transcription Factors (metabolism) Bone Morphogenetic Protein 4 Bone Morphogenetic Proteins (pharmacology) Fibroblast Growth Factor 2 (pharmacology) Gene Expression Regulation, Neoplastic (physiology) Homeodomain Proteins (metabolism) Humans Immunohistochemistry Intermediate Filament Proteins (metabolism) Mice Mice, Nude Nerve Growth Factors (metabolism) Nerve Tissue Proteins (drug effects, metabolism) Nestin Receptor, Nerve Growth Factor (metabolism) Receptors, Retinoic Acid (metabolism) Recombinant Proteins (pharmacology) Reverse Transcriptase Polymerase Chain Reaction S100 Calcium Binding Protein beta Subunit S100 Proteins (metabolism) Sarcoma, Synovial (metabolism, pathology) Signal Transduction (physiology) Transcription Factor HES-1 Tretinoin (pharmacology) Tumor Cells, Cultured Xenograft Model Antitumor Assays

Join CureHunter, for free Research Interface BASIC access!

Take advantage of free CureHunter research engine access to explore the best drug and treatment options for any disease. Find out why thousands of doctors, pharma researchers and patient activists around the world use CureHunter every day.

Realize the full power of the drug-disease research graph!