抗がん剤のｍｏｌｅｃｕｌａｒ　ｔａｒｇｅｔｉｎｇ　　細胞浸潤・増殖因子

DOI 参考文献18件
  • 青木 淳賢
    東京大学大学院薬学系研究科衛生化学教室
  • 岸 安宏
    東京大学大学院薬学系研究科衛生化学教室

書誌事項

タイトル別名
  • Autotaxin has lysophospholipase D activity leading to tumor cell growth and motility by lysophosphatidic acid production
  • Autotaxin has lysophospholipase D activity leading to tumor cell growth and motility by lysophosplealidic acid production
  • 細胞浸潤·増殖因子
公開日
2003
DOI
  • 10.2745/dds.18.361
公開者
日本DDS学会

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説明

Autotaxin (ATX) is a tumor cell motility-stimulating factor, originally isolated from melanoma cell supernatants. ATX had been proposed to mediate its effects through 5'-nucleotide pyrophosphatase and phosphodiesterase activities. However, the ATX substrate mediating the increase in cellular motility remains to he identified. Here, we demonstrated that lysophospholipase D (lysoPLD) purified from fetal bovine serum, which catalyzes the production of the bioactive phospholipid mediator, lysophosphatidic acid (LPA), from lysophosphatidylcholine(LPC), is identical to ATX. The Km value of ATX for LPC was 25-fold lower than that for the synthetic nucleoside substrate, p-nitrophenyl-tri-monophosphate. LPA mediates multiple biological functions including cytoskeletal reorganization, chemotaxis and cell growth through activation of specific G-protein-coupled receptors. Recombinant ATX, particularly in the presence of LPC, dramatically increased chemotaxis and proliferation of multiple different cell lines. Moreover, we demonstrate that several cancer cell lines release significant amounts of LPC, a substrate for ATX, into the culture medium. The demonstration that ATX and lysoPLD are identical suggests that autocrine or paracrine production of LPA contributes to tumor cell motility, survival and proliferation. It also provides potential novel targets for therapy of pathophysiological states, including cancer.

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