title: Constitutively active lysophosphatidic acid receptor-1 enhances the induction of matrix metalloproteinase-2.
abstract: Lysophosphatidic acid (LPA) is a simple phospholipid which interacts with at least six G protein-coupled transmembrane LPA receptors (LPA(1)-LPA(6)). In rat neuroblastoma B103 cells, we have recently reported that each LPA receptor indicates the different cellular functions, including cell motility, invasion and tumorigenicity. Especially, mutated and constitutively active LPA(1) enhanced these cellular effects in B103 cells. In the present study, to better understand a role of mutated LPA(1) underlying progression of cancer cells, we measured the expression and activity levels of matrix metalloproteinases (MMPs) in constitutively active mutant Lpar1-expressing B103 cells (lpa1Δ-1), compared with each wild-type LPA receptor-expressing cells. LPA receptor-unexpressing cells were also used as control. In quantitative real time RT-PCR analysis, the expressions of Mmp-9 were detected at the same levels in all cells. By contrast, Mmp-2 expressions of lpa1Δ-1 were significantly higher than those of other cells. In gelatin zymography, proMmp-9 was observed at the same levels in all cells. Interestingly, markedly high levels of proMmp-2 and Mmp-2 were detected in lpa1Δ-1 cells, whereas no activation was in other cells. The increased expression and activity of Mmp-2 in lpa1Δ-1 cells were suppressed by the pretreatment with a Gq protein inhibitor. These results suggest that mutated LPA(1) may involve in the enhancement of Mmp-2 expression and activation in rat neuroblastoma cells.
authors.affiliation: Division of Cancer Biology and Bioinformatics, Department of Life Science, Faculty of Science and Engineering, Kinki University, 3-4-1, Kowakae, Higashiosaka, Osaka 577-8502, Japan.
authors.forename: Kohei
authors.initials: K
authors.lastname: Kato
authors.forename: Rie
authors.initials: R
authors.lastname: Fukui
authors.forename: Kyoko
authors.initials: K
authors.lastname: Okabe
authors.forename: Eriko
authors.initials: E
authors.lastname: Tanabe
authors.forename: Misaho
authors.initials: M
authors.lastname: Kitayoshi
authors.forename: Nobuyuki
authors.initials: N
authors.lastname: Fukushima
authors.forename: Toshifumi
authors.initials: T
authors.lastname: Tsujiuchi
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D004789:Enzyme Activation; D020778:Matrix Metalloproteinase 2 / Q000096:biosynthesis* / Q000235:genetics; D020780:Matrix Metalloproteinase 9 / Q000096:biosynthesis / Q000235:genetics; D009361:Neoplasm Invasiveness; D009447:Neuroblastoma / Q000201:enzymology* / Q000235:genetics / Q000473:pathology; D051381:Rats; D049368:Receptors, Lysophosphatidic Acid / Q000235:genetics / Q000378:metabolism*
chemical_list: D049368:Receptors, Lysophosphatidic Acid; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9