title: ETV5 as a regulator of matrix metalloproteinase 2 in human chondrosarcoma.
abstract: Chondrosarcoma is a unique type of bone cancer in that it does not respond to chemotherapy or radiation therapy, and therefore many affected patients die from metastatic disease. Metastasis has been correlated with the upregulation of the matrix metalloproteinase (MMP) family of proteases, which can degrade extracellular components. ETV5 is a transcription factor which has shown to be overexpressed in various types of invasive tumors. We hypothesized that ETV5 regulates MMP2 in human chondrosarcoma with the protease acting as a downstream effector. Gene knock-down of ETV5 in human chondrosarcoma cells reduces MMP2 mRNA expression as well as decreased protein production and significantly decreased MMP2 activity. With plasmid transfected ETV5 upregulation, MMP2 expression is similarly upregulated at the gene expression and protein levels. Data from our bone resorption studies revealed that when a matrix metalloproteinase-2 inhibitor is added to the growth media of chondrosarcoma cells, collagen released from bone chips incubated with the cells decreased by 27%. This data suggests that ETV5 has a significant role in regulating MMP2 expression and therefore matrix resorption in human chondrosarcoma, and thus may be a targetable upstream effector of the metastatic cascade in this cancer.
authors.affiliation: Department of Health Science Graduate Studies, McMaster University, Hamilton, Ontario, Canada.
authors.forename: Patricia F
authors.initials: PF
authors.lastname: Power
authors.forename: Isabella W Y
authors.initials: IW
authors.lastname: Mak
authors.forename: Shalini
authors.initials: S
authors.lastname: Singh
authors.forename: Snezana
authors.initials: S
authors.lastname: Popovic
authors.forename: Rebecca
authors.initials: R
authors.lastname: Gladdy
authors.forename: Michelle
authors.initials: M
authors.lastname: Ghert
mesh_terms: D001859:Bone Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D001862:Bone Resorption / Q000378:metabolism* / Q000473:pathology; D002460:Cell Line; D045744:Cell Line, Tumor; D002813:Chondrosarcoma / Q000235:genetics / Q000378:metabolism* / Q000556:secondary; D003094:Collagen / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D015972:Gene Expression Regulation, Neoplastic / Q000502:physiology; D006801:Humans; D020778:Matrix Metalloproteinase 2 / Q000235:genetics / Q000378:metabolism*; D010006:Osteoblasts / Q000166:cytology / Q000378:metabolism; D034741:RNA, Small Interfering / Q000235:genetics; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*
chemical_list: D004268:DNA-Binding Proteins; C086680:ETV5 protein, human; D004791:Enzyme Inhibitors; D034741:RNA, Small Interfering; D014157:Transcription Factors; D003094:Collagen; C522361:MMP2 protein, human; D020778:Matrix Metalloproteinase 2