Abstract：
:Autotaxin (ATX) is an exoenzyme that potently induces tumor cell motility, and enhances experimental metastasis and angiogenesis. ATX was shown recently to be identical to serum lysophospholipase D activity, producing lysophosphatidic acid (LPA) from lyso-glycerophospholipids. LPA, itself a strong chemoattractant for tumor cells, may mediate the actions of ATX. We now extend the substrate specificity to sphingosylphosphorylcholine (SPC), which ATX hydrolyzes to sphingosine-1-phosphate (S1P). Under migration assay conditions, this novel reaction for the production of S1P has a substrate (SPC) K(m) = 0.23 +/- 0.07 mM. In our responder cell lines (NIH3T3 clone7 and A2058), S1P exerts maximal biological effects at concentrations of 10-100 nM and is mimicked in its biological effects by ATX plus SPC. These effects include inhibition of ATX- and LPA-stimulated motility, and elevation of activated Rho. In NIH3T3 clone7 cells stimulated with platelet-derived growth factor and treated with 10-25 nM S1P, motility is not inhibited and activation of Rho is unaffected, indicating that S1P possesses specificity in its effects. The exoenzyme ATX can potentially regulate diverse processes such as motility and angiogenesis via the S1P family of receptors. Because ATX hydrolyzes nucleotides, lyso-glycerophospholipids, and phosphosphingolipids into bioactive products, it possesses the ability, depending on the availability of substrates, to act as positive or negative regulator of receptor-mediated activity in the cellular microenvironment.
journal_name
Cancer Resjournal_title
Cancer researchauthors
Clair T,Aoki J,Koh E,Bandle RW,Nam SW,Ptaszynska MM,Mills GB,Schiffmann E,Liotta LA,Stracke MLsubject
Has Abstractpub_date
2003-09-01 00:00:00pages
5446-53issue
17eissn
0008-5472issn
1538-7445journal_volume
63pub_type
杂志文章相关文献
CANCER RESEARCH文献大全abstract：:The ubiquitin proteasome system is responsible for the proteolysis of important cell cycle and apoptosis-regulatory proteins. In this paper we report that the dipeptidyl proteasome inhibitor, phthalimide-(CH2)8CH-(cyclopentyl) CO-Arg(NO2)-Leu-H (CEP1612), induces apoptosis and inhibits tumor growth of the human lung c...
journal_title：Cancer research
pub_type： 杂志文章
doi：
更新日期：2001-02-15 00:00:00
abstract：:We demonstrate that a mouse-human chimeric anti-ganglioside GD2-interleukin (IL)-2 fusion protein (ch14.18-IL2) substantially amplifies tumor-protective immunity against murine melanoma induced by an autologous oral DNA vaccine containing the murine ubiquitin gene fused to murine melanoma peptide epitopes gp100(25-35)...
journal_title：Cancer research
pub_type： 杂志文章
doi：
更新日期：2001-08-15 00:00:00
abstract：:The interactions of tumorigenic cells with the extracellular matrix play a critical role in the establishment of metastases. Thrombospondin (TSP) is prominent at sites of tissue injury and promotes the attachment, spreading, and motility of several cell types. We have investigated the relationship between human carcin...
journal_title：Cancer research
pub_type： 杂志文章
doi：
更新日期：1993-01-15 00:00:00
abstract：:The interaction between platelets and tumor cells is important in the formation of pulmonary metastasis. We previously established the 8F11 monoclonal antibody (mAb) by immunizing rats with the NL-17 cell line, a highly metastatic variant of mouse colon adenocarcinoma 26. 8F11 could inhibit the platelet aggregation in...
journal_title：Cancer research
pub_type： 杂志文章
doi：
更新日期：1997-07-15 00:00:00
abstract：:We report that tumor necrosis factor (TNF) alpha induced a strong antitumor immune reaction when it was produced in arteries leading to tumors by gene transfer in vivo. We used a mouse model carrying a sarcoma-180 tumor in the right footpad and injected the fusogenic liposomes encapsulating the human TNF-alpha gene in...
journal_title：Cancer research
pub_type： 杂志文章
doi：
更新日期：1998-12-15 00:00:00
abstract：:Both nonsteroidal anti-inflammatory drugs (NSAIDs) and cyclooxygenase (COX) 2-selective inhibitors such as celecoxib are being reported as having potent anticancer activity in laboratory models. Several reports have suggested that the mechanism of action of these agents in reducing tumor volume/burden is unrelated to ...
journal_title：Cancer research
pub_type： 杂志文章
doi：
更新日期：2002-11-15 00:00:00
abstract：:Prostate-specific membrane antigen (PSMA), initially defined by monoclonal antibody (mAb) 7E11, is a now well-characterized type 2 integral membrane glycoprotein expressed in a highly restricted manner by prostate epithelial cells. 7E11 has been shown to bind an intracellular epitope of PSMA that, in viable cells, is ...
journal_title：Cancer research
pub_type： 杂志文章
doi：
更新日期：1997-09-01 00:00:00
abstract：:CD4+ T-cell responses against human tumor antigens are a potentially critical component of the antitumor immune response. Molecular methods have been devised for rapidly identifying MHC class II-restricted tumor antigens and elucidating the recognized epitopes. We describe here the identification of neo-poly(A) polyme...
journal_title：Cancer research
pub_type： 杂志文章
doi：
更新日期：2002-10-01 00:00:00
abstract：:Treatment of 9L rat brain tumor cells with 1.0 mM alpha-difluoromethylornithine (DFMO) produced a time-dependent depletion of cellular putrescine and spermidine. An increase in the potentiation of 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU) cytotoxicity, measured with a colony-forming efficiency assay, followed the ti...
journal_title：Cancer research
pub_type： 杂志文章
doi：
更新日期：1984-05-01 00:00:00
abstract：:Sixteen clones (RASK-1 to -16) of murine monoclonal antibodies were raised against ras Mr 21,000 protein (p21). The p21 produced by Escherichia coli with inserted v-Ki-ras genes was used as immunogen. RASK-1 was found to be specific for Ki-ras p21, whereas RASK-2 to -16 reacted with the p21s of Ki-, N-, and Ha-ras gen...
journal_title：Cancer research
pub_type： 杂志文章
doi：
更新日期：1988-10-01 00:00:00
abstract：:The effect of 5-S-cysteinyl-L-3,4-dihydroxyphenylalanine (cys-dopa), an intermediate in the pathway from L-3,4-dihydroxyphenylalanine (L-dopa) to pheomelanin, on the growth of eight human tumor cell lines in culture was compared to that of L-dopa. The tumor cell lines tested comprise two neuroblastomas (NB-1 and YT-nu...
journal_title：Cancer research
pub_type： 杂志文章
doi：
更新日期：1980-07-01 00:00:00
abstract：:The Salmonella-microsome assay for mutagenesis was used to determine the effect of ozone on the mutagenesis of selected carcinogens and mutagens in water. Short periods of ozonation were shown to completely inactivate the mutagenicity of several polyaromatic amine mutagens including acriflavine, proflavine, and beta-n...
journal_title：Cancer research
pub_type： 杂志文章
doi：
更新日期：1979-06-01 00:00:00
abstract：:The high mortality of pancreatic cancer demands that new therapeutic avenues be developed. The orally available small-molecule inhibitor AT13148 potently inhibits ROCK1 and ROCK2 kinases that regulate the actomyosin cytoskeleton. We previously reported that ROCK kinase expression increases with human and mouse pancrea...
journal_title：Cancer research
pub_type： 杂志文章
doi：10.1158/0008-5472.CAN-17-1339
更新日期：2018-06-15 00:00:00
abstract：:The ability of osteosarcoma cells to form lung metastases has been inversely correlated to cell surface Fas expression. Downregulation of Fas allows osteosarcoma cells to circumvent FasL-mediated apoptosis upon entrance into the FasL(+) lung microenvironment. However, the mechanism of Fas regulation remains unclear. H...
journal_title：Cancer research
pub_type： 杂志文章
doi：10.1158/0008-5472.CAN-11-1460
更新日期：2012-02-15 00:00:00
abstract：:2-Amino-l-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) is a mutagenic and carcinogenic heterocyclic amine present in pyrolysate products of meat and fish and has been shown to induce tumors in the colon, mammary gland, and possibly lymphatic system. Experiments were designed to examine the lymphoma-inducing capacity o...
journal_title：Cancer research
pub_type： 杂志文章
doi：
更新日期：1996-08-01 00:00:00
abstract：:The idea of using oncolytic viruses for the treatment of cancers was proposed a century ago. During the last two decades, viruses able to replicate specifically in cancer cells and to induce their lysis were identified and were genetically modified to improve their viro-oncolytic properties. More recently, a new appro...
journal_title：Cancer research
pub_type： 杂志文章
doi：10.1158/0008-5472.CAN-05-1076
更新日期：2005-10-15 00:00:00
abstract：:The tumor suppressor gene p53 regulates G1 checkpoint prior to the initiation of DNA synthesis, which can either induce G1 arrest or signal apoptosis. The involvement of p53 in apoptosis may also be related to its ability to down-regulate transcription of the bcl-2 gene. The bcl-2 gene product prevents most types of a...
journal_title：Cancer research
pub_type： 杂志文章
doi：
更新日期：1995-10-15 00:00:00
abstract：:Interleukin-2-based regimens of biological therapy have shown some clinical promise for the treatment of kidney cancer in humans, although the mechanisms responsible for tumor regression occurring in these patients remain unclear. Preclinical insight into these mechanisms is limited by a paucity of orthotopic animal m...
journal_title：Cancer research
pub_type： 杂志文章
doi：
更新日期：2001-08-15 00:00:00
abstract：:Although interleukin-15 (IL-15) is a powerful immunomodulatory factor that has been proposed for cancer immunotherapy, its intratumoral expression may be correlated with tumor progression and/or poor clinical outcome. Therefore, neoplasias potentially sensitive to immunotherapy should be checked for their IL-15 expres...
journal_title：Cancer research
pub_type： 杂志文章
doi：10.1158/0008-5472.CAN-08-3198
更新日期：2009-02-15 00:00:00
abstract：:Receptor for advanced glycation end products (RAGE) and its ligands are overexpressed in multiple cancers. RAGE has been implicated in tumorigenesis and metastasis, but little is known of the mechanisms involved. In this study, we define a specific functional role for an alternate splice variant termed RAGE splice var...
journal_title：Cancer research
pub_type： 杂志文章
doi：10.1158/0008-5472.CAN-10-0595
更新日期：2010-07-01 00:00:00
abstract：:Two subclones of L1210 murine leukemia (L1210-46.1 and L1210-56.3) were isolated in the absence of selective agents. Subclone 56.3 appeared to be more sensitive than was subclone 46.1 to treatment with dexamethasone, 1-beta-D-arabinofuranosyl cytosine, vincristine, and X-irradiation. No differences between the parent ...
journal_title：Cancer research
pub_type： 杂志文章
doi：
更新日期：1983-06-01 00:00:00
abstract：:Camptothecin, which induces an unusual type of DNA damage by trapping cellular topoisomerase I on chromosomal DNA in the form of drug-enzyme-DNA cleavable complexes, inhibits DNA synthesis and specifically kills S-phase cells. Cotreatment of L1210 cells with aphidicolin, which is an inhibitor of replicative DNA polyme...
journal_title：Cancer research
pub_type： 杂志文章
doi：
更新日期：1989-09-15 00:00:00
abstract：:Proline is a readily released stress substrate that can be metabolized by proline oxidase (POX) to generate either reactive oxygen species (ROS) to induce apoptosis or autophagy or ATP during times of nutrient stress. However, the contribution of proline metabolism to tumorigenesis in hypoxic microenvironments has not...
journal_title：Cancer research
pub_type： 杂志文章
doi：10.1158/0008-5472.CAN-12-0080
更新日期：2012-07-15 00:00:00
abstract：:Mechanism, in addition to protein kinase C activation may mediate 12-O-tetradecanoylphorbol-13-acetate (TPA) stimulated differentiation of leukemic cells. We compared the effect of pretreating intact monoblastoid U937 cells with TPA or the diacylglycerol derivative, 1-oleoyl-2-acetylglycerol (OAG), by studying the pro...
journal_title：Cancer research
pub_type： 杂志文章
doi：
更新日期：1987-07-01 00:00:00
abstract：:The intention of this study was to estimate the pharmacological advantage of a clinically applicable method of isolated liver perfusion (ILP) over hepatic artery infusion (HAI) administering various doses of 5-fluorouracil (FUra). FUra concentrations were measured using high-performance liquid chromatography in liver ...
journal_title：Cancer research
pub_type： 杂志文章
doi：
更新日期：1991-03-15 00:00:00
abstract：:Recent technologic advances have permitted higher resolution and more rapid analysis of individual cancer genomes at the single-nucleotide level. Such advances have shown bewildering intertumor heterogeneity with limited somatic alterations shared between tumors of the same histopathologic subtype. Exacerbating such c...
journal_title：Cancer research
pub_type： 杂志文章,评审
doi：10.1158/0008-5472.CAN-12-2217
更新日期：2012-10-01 00:00:00
abstract：:Members of the phosphatidylinositol 3-kinase-related kinase family, in particular the ataxia-telangiectasia mutated (ATM) kinase and the catalytic subunit of the DNA-dependent protein kinase (DNA-PKcs), regulate cellular responses to DNA double-strand breaks. Increased sensitivity to ionizing radiation (IR) in DNA-PKc...
journal_title：Cancer research
pub_type： 杂志文章
doi：10.1158/0008-5472.CAN-07-0675
更新日期：2008-01-01 00:00:00
abstract：:Resistance of human renal cell carcinoma (RCC) and melanoma to the apoptosis-inducing effects of IFNs was postulated to result from epigenetic silencing of genes by DNA methylation, a common feature of human cancers. To reverse silencing, 5-AZA-deoxycytidine (5-AZA-dC) or selective depletion of DNA methyltransferase 1...
journal_title：Cancer research
pub_type： 杂志文章
doi：10.1158/0008-5472.CAN-05-2303
更新日期：2006-03-01 00:00:00
abstract：:HT-29 cells express and secrete insulin-like growth factor (IGF)-II and only one of the six IGF-binding proteins, IGFBP-4. In the present study, the physiological role of endogenous IGFBP-4 in regulating the growth response of HT-29 cells to exogenous and endogenous IGFs was examined. Both the basal and the IGF-stimul...
journal_title：Cancer research
pub_type： 杂志文章
doi：
更新日期：1994-12-15 00:00:00
abstract：:Upon incubation of cultured mammalian cells with the new anthracycline analogues cyanomorpholinyldoxorubicin and morpholinyldoxorubicin, nucleoli irreversibly segregate into their substructures which form individual portions of the nucleolar mass and characteristic electron-dense components adjacent to the nucleolonem...
journal_title：Cancer research
pub_type： 杂志文章
doi：
更新日期：1988-07-15 00:00:00
