2006 Fiscal Year Final Research Report Summary
Patho-Physiological role of lysophosphatidic acid.
| Project/Area Number |
17390016
|
|---|
| Research Category |
Grant-in-Aid for Scientific Research (B)
|
| Allocation Type | Single-year Grants |
|---|
| Section | 一般 |
|---|
| Research Field |
Biological pharmacy
|
|---|
| Research Institution | The University of Tokyo |
|---|
Principal Investigator |
AOKI Junken The University of Tokyo, Graduate School of Pharmaceutical Sciences, Associate Professor, 大学院薬学系研究科, 助教授 (20250219)
|
|---|
| Project Period (FY) |
2005 – 2006
|
| Keywords | lysophosphatidic acid / LPA / lysophospholipase D / lysoPLD / lysophosphatidylcholine / LPC |
|---|
| Research Abstract |
Glioblastoma multiforme (GBM) is the most malignant glioma because of its high infiltration into the normal brain parenchyma. Factors that influence the motility of GBM cells are of particular interest because GBM cells are highly invasive. We recently showed that autotaxin (ATX), a potent cell motility-stimulating factor that was originally isolated from melanoma cells, has lysophospholipase D activity. Lysophospholipase D produces a bioactive phospholipid, lysophosphatidic acid (LPA), from lysophosphatidylcholine (LPC), and regulates cell motility through G protein-coupled receptors for LPA. In this study we found that ATX is highly expressed in GBM tissues but not in tissues from other brain tumors. In addition, LPA_1, an LPA receptor responsible for LPA-driven cell motility, is predominantly expressed in GBM. Among 50 tumor cell lines derived from various tissues, several cell lines, especially glioblastoma, express a significant amount of ATX at both the mRNA and protein levels. These cells were also found to express LPA_1 mRNA predominantly and showed LPA_1-dependent cell migration in response to LPA and ATX in the Boyden-chamber assay. The glioblastoma that showed the highest ATX expression (SNB-78), as well as ATX-stable transfectants showed LPA_1-dependent cell migration in response to both LPA and LPC in both the Boyden-chamber and a wound healing assays. The LPA_1-dependent cell migration was completely abolished by an LPA_1-antagonist, Ki16425. Our results suggest that the autocrine production of LPA by cancer cell-derived ATX and exogenous LPC contribute to the invasiveness of GBM cells and that LPA_1, ATX and LPC-producing enzymes are potential targets for GBM therapy.
|
-
-
-
-
-
-
-
-
-
-
-
-
[Journal Article] Transgenic Expression of Group V, but not Group X, Secreted Phospholipase A2 in Mice Leads to Neonatal Lethality due to Lung Dysfunction2006
Author(s)
M.Ohtsuki, Y.Taketomi, S.Arata, S.Masuda, Y.Ishikawa, T.Ishii, Y.Takanezawa, J.Aoki, H.Arai, K.Yamamoto, I.Kudo, M.Murakami
-
Journal Title
J.Biol.Chem. 281
Pages: 36420-36433
Description
「研究成果報告書概要(欧文)」より
