title: Downregulation of ERK signaling impairs U2OS osteosarcoma cell migration in collagen matrix by suppressing MMP9 production.
abstract: The present study investigated the role of extracellular signal-regulated kinase (ERK) activation in the migratory phenotype of human U2OS osteosarcoma (OS) cells in a collagen matrix. The activation of ERK was inhibited by PD98059, a specific inhibitor of ERK kinase. Additionally, no significant differences were observed in the adhesion and proliferation of the cells with or without PD98059 treatment in collagen-coated dishes. The migratory capacity of the U2OS cells was then examined in non-coated and collagen-coated dishes, and the results depicted that collagen I enhanced the migration of the U2OS cells, the effect of which was significantly blocked by the treatment of the cells with PD98059. Furthermore, enhanced gene and protein expression of matrix metalloproteinase 9 (MMP9), but not MMP2, was observed to be involved in the enhanced migratory phenotype of the U20S cells in the collagen-coated plates. This effect was partially abolished by the treatment of the cells in the collagen-coated dishes with ERK inhibitor. Collectively, the data demonstrate that ERK signaling is important for the migration of U2OS cells through the extracellular matrix (ECM), which is comprised mostly of collagen, by enhancing MMP9 production. These results may contribute to the regulation of MMP9 production in metastatic OS.
authors.affiliation: Department of Immunology and Institute of Medical Sciences, Chonbuk National University Medical School, Jeonju, Jeonbuk 561-756, Republic of Korea.
authors.forename: Barun
authors.initials: B
authors.lastname: Poudel
authors.affiliation: Department of Oriental Pharmacy, College of Pharmacy, Wonkwang University, Iksan 570-749, Republic of Korea.
authors.forename: DO-Kuk
authors.initials: DK
authors.lastname: Kim
authors.affiliation: Department of Immunology and Institute of Medical Sciences, Chonbuk National University Medical School, Jeonju, Jeonbuk 561-756, Republic of Korea.
authors.forename: Hyeon-Hui
authors.initials: HH
authors.lastname: Ki
authors.affiliation: Department of Pharmacology, Chonbuk National University Medical School, Jeonju 561-756, Republic of Korea.
authors.forename: Young-Bae
authors.initials: YB
authors.lastname: Kwon
authors.affiliation: Department of Oriental Pharmacy, College of Pharmacy, Wonkwang University, Iksan 570-749, Republic of Korea.
authors.forename: Young-Mi
authors.initials: YM
authors.lastname: Lee
authors.affiliation: Department of Immunology and Institute of Medical Sciences, Chonbuk National University Medical School, Jeonju, Jeonbuk 561-756, Republic of Korea.
authors.forename: Dae-Ki
authors.initials: DK
authors.lastname: Kim
keywords: PD98059; U2OS; extracellular signal-regulated kinase; matrix metalloproteinase 9; osteosarcoma