Lysophosphatidic Acid and Autotaxin Stimulate Cell Motility of Neoplastic and Non-neoplastic Cells through LPA1

Hama, Kotaro; Aoki, Junken; Fukaya, Masahiro; Kishi, Yasuhiro; Sakai, Teruyuki; Suzuki, Rika; Ohta, Hiroyuki; Yamori, Takao; Watanabe, Masahiko; Chun, Jerold; Arai, Hiroyuki

doi:10.1074/jbc.m313927200

Cited by 260 publications

(213 citation statements)

References 36 publications

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“…LPA, through LPA 1 receptor, stimulated glioma cell migration, while S1P, through S1P 2 receptor, negatively regulated the LPA action. LPA 1 -receptor-mediated migration has also been shown in the glioblastoma cell lines SF295 and SF539 (Hama et al, 2004). Previously, we reported that brain is one tissue in which S1P is abundantly present .…”

Section: Discussionmentioning

confidence: 95%

“…Furthermore, LPA acts as an autocrine growth factor, and one or more LPA receptors are expressed in the prostate cancer cells (Xie et al, 2002). In astroglial cells as well, extracellularly added LPA induces the proliferation and migration of stimulated cells (Manning et al, 2000;Steiner et al, 2002;Malchinkhuu et al, 2003;Hama et al, 2004). Although there are enough studies related to LPAstimulated cell migration, the details of LPA signaling in migration have not been elucidated so far.…”

Section: Introductionmentioning

confidence: 99%

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Role of p38 mitogen-activated kinase and c-Jun terminal kinase in migration response to lysophosphatidic acid and sphingosine-1-phosphate in glioma cells

et al. 2005

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A potential role for 1-oleoyl-sn-glycero-3-phosphate or lysophosphatidic acid (LPA) and sphingosine-1-phosphate (S1P) in the regulation of malignant diseases has been widely considered. In this study, we found that in transformed astroglial cells, the expression profile of lysophospholipid receptor mRNA and the action modes of LPA and S1P on cell motility were changed: there was a change in the acquisition of the ability of LPA to stimulate cell migration and a change in the migratory response to S1P from stimulation through S1P 1 to inhibition through S1P 2 . LPA-induced cell migration was almost completely inhibited by either pertussis toxin, LPA 1 receptor antagonists including Ki16425 (3-(4-[4-([1-(2-chlorophenyl)ethoxy]carbonyl amino)-3-methyl-5-isoxazolyl] benzylsulfonyl)propanoic acid) or an inhibitor of phosphatidylinositol 3-kinase (PI3K) wortmannin. The LPA-induced action was also suppressed, although incompletely, by several specific inhibitors for intracellular signaling pathways including Rac1, Cdc42, p38 mitogen-activated protein kinase (p38MAPK) and c-Jun terminal kinase (JNK), but not extracellular signalregulated kinase. Nearly complete inhibition of migration response to LPA, however, required simultaneous inhibition of both the p38MAPK and JNK pathways. Inhibition of Rac1 suppressed JNK but not p38MAPK, while the activity of p38MAPK was abolished by a dominantnegative form of Cdc42. These findings suggest that, in glioma cells, the PI3K/Cdc42/p38MAPK and PI3K/ Rac1/JNK pathways are equally important for LPA 1 receptor-mediated migration.

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Section: Discussionmentioning

confidence: 95%

Section: Introductionmentioning

confidence: 99%

Role of p38 mitogen-activated kinase and c-Jun terminal kinase in migration response to lysophosphatidic acid and sphingosine-1-phosphate in glioma cells

et al. 2005

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“…The cell motility-inducing activity of NPP2 depends on the production of bioactive lipids [384][385][386]. It is now thought that the major physiological functions of NPP2 result from its phospholipase activity [387].…”

Section: General Properties and Functional Rolementioning

confidence: 99%

Cellular function and molecular structure of ecto-nucleotidases

Zimmermann

Zebisch

Sträter

2012

Purinergic Signalling

888

922

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Ecto-nucleotidases play a pivotal role in purinergic signal transmission. They hydrolyze extracellular nucleotides and thus can control their availability at purinergic P2 receptors. They generate extracellular nucleosides for cellular reuptake and salvage via nucleoside transporters of the plasma membrane. The extracellular adenosine formed acts as an agonist of purinergic P1 receptors. They also can produce and hydrolyze extracellular inorganic pyrophosphate that is of major relevance in the control of bone mineralization. This review discusses and compares four major groups of ectonucleotidases: the ecto-nucleoside triphosphate diphosphohydrolases, ecto-5′-nucleotidase, ecto-nucleotide pyrophosphatase/phosphodiesterases, and alkaline phosphatases. Only recently and based on crystal structures, detailed information regarding the spatial structures and catalytic mechanisms has become available for members of these four ecto-nucleotidase families. This permits detailed predictions of their catalytic mechanisms and a comparison between the individual enzyme groups. The review focuses on the principal biochemical, cell biological, catalytic, and structural properties of the enzymes and provides brief reference to tissue distribution, and physiological and pathophysiological functions.

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“…Ki16425 blocks the LPA-induced motility of various LPA 1 -expressing carcinoma cell lines in vitro (18). Ki16425 also dosedependently inhibited LPA-induced proliferation of LPA 1 -expressing MDA-BO2͞GFP and CHO␤ 3 wt cell lines in vitro (Fig.…”

Section: Progression 3-(4-[4-([1-(2-chlorophenyl)ethoxy]carbonyl Amimentioning

confidence: 99%

The type 1 lysophosphatidic acid receptor is a target for therapy in bone metastases

Boucharaba

Serre

Guglielmi

et al. 2006

Proc. Natl. Acad. Sci. U.S.A.

190

162

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Platelet-derived lysophosphatidic acid (LPA) supports the progression of breast and ovarian cancer metastasis to bone. The mechanisms through which LPA promotes bone metastasis formation are, however, unknown. Here we report that silencing of the type 1 LPA receptor (LPA 1) in cancer cells blocks the production of tumor-derived cytokines that are potent activators of osteoclastmediated bone destruction and significantly reduces the progression of osteolytic bone metastases. Moreover, functional blockade of LPA action on its cognate receptor LPA 1 using a pharmacological antagonist mimics the effects of silencing LPA 1 in tumor cells in vitro and substantially reduces bone metastasis progression in animals. Overall, these results suggest that inhibition of plateletderived LPA action on LPA 1 expressed by tumor cells may be a promising therapeutic target for patients with bone metastases.breast cancer ͉ platelet ͉ treatment B one is a frequent metastatic site for many cancers (1). Bone metastasis formation is associated with a high morbidity rate because of intractable bone pain, pathological fractures, hypercalcemia, and nerve compression (1). Bone-residing metastatic cells are not directly able to destroy bone. Instead, they secrete paracrine factors [IL-6, IL-8, and parathyroid hormone-related peptide (PTHrP)] that stimulate osteoblast-mediated bone resorption, leading to osteolysis (1). In this respect, bisphosphonates (as inhibitors of osteoclast activity) are the standard of care in the treatment of patients with bone metastases. Unfortunately, these treatments are only palliative and do not provide a life-prolonging benefit to metastatic patients (2), indicating that more efficacious therapies are required.We have recently demonstrated that the naturally occurring bioactive lipid, lysophosphatidic acid (LPA), produced by activated blood platelets (3), is coopted by breast and ovarian cancer cells as a tumor mitogen and an inducer of tumor-derived cytokine (IL-6 and IL-8) that, altogether, promote the progression of bone metastases (4). Endogenous receptors through which LPA promotes breast cancer progression and bone metastasis are, however, unknown. LPA binds to three GTPbinding protein-coupled receptors, LPA 1 (5), LPA 2 (6), and LPA 3 (7), that mediate the growth factor-like activity of LPA in a large variety of cell types in culture, including cancer cells (8). Interestingly, mRNA levels for LPA receptors are up-regulated in various cancers (9-11). Yet, the clinical significance of such observations remains to be determined. Using both genetic and pharmacological approaches in vitro and in vivo, we demonstrate here that inhibition of LPA action on its receptor LPA 1 is a promising therapeutic target in cancer, especially for metastasis to bone.

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Lysophosphatidic Acid and Autotaxin Stimulate Cell Motility of Neoplastic and Non-neoplastic Cells through LPA1

Cited by 260 publications

References 36 publications

Role of p38 mitogen-activated kinase and c-Jun terminal kinase in migration response to lysophosphatidic acid and sphingosine-1-phosphate in glioma cells

Role of p38 mitogen-activated kinase and c-Jun terminal kinase in migration response to lysophosphatidic acid and sphingosine-1-phosphate in glioma cells

Cellular function and molecular structure of ecto-nucleotidases

The type 1 lysophosphatidic acid receptor is a target for therapy in bone metastases

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