{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,23]],"date-time":"2025-10-23T05:17:43Z","timestamp":1761196663640,"version":"build-2065373602"},"reference-count":54,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2005,9,19]],"date-time":"2005-09-19T00:00:00Z","timestamp":1127088000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cell Biochemistry &amp;amp; Function"],"published-print":{"date-parts":[[2006,1]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Immunosuppression is a life\u2010threatening complication of late cancer stages. In this regard, overproduction in the host plasma of the anti\u2010inflammatory cyclopentenone prostaglandins (CP\u2010PGs), which are strongly antiproliferative at high concentrations, may impair immune function. In fact, lymphoid tissues of tumour\u2010bearing rats accumulated large amounts of CP\u2010PGs while the tumour tissue itself did not. Expression of the CP\u2010PG\u2010induced 72\u2010kDa heat shock protein (hsp70) was elevated in lymphocytes from tumour\u2010bearing animals related to controls. As the capacity for CP\u2010PG uptake by lymphocytes is the same as tumour cells, we investigated whether the latter could overexpress the multidrug resistance\u2010associated protein (<jats:italic>MRP1<\/jats:italic>\/GS\u2010X pump) which extrudes CP\u2010PGs towards the extracellular space as glutathione <jats:italic>S<\/jats:italic>\u2010conjugates. Walker 256 tumour cells extruded 15\u2010fold more S\u2010conjugates than lymphocytes from the same rats (<jats:italic>p<\/jats:italic>\u2009&lt;\u20090.001). This did not appear to be related to deficiency in lymphocyte glutathione (GSH) metabolism, since the major GSH metabolic routes are consistent with CP\u2010PG conjugation in lymphocytes. This was not the case, however, for the <jats:italic>MRP1<\/jats:italic>\/GS\u2010X pump activity in lymphocyte membranes (in pmol\/min\/mg protein: 3.1\u2009\u00b1\u20091.7 from normal rats, 0.2\u2009\u00b1\u20090.2 from tumour\u2010bearing animals vs 64.3\u2009\u00b1\u20097.0 in tumour cells) which was confirmed by Western blot analysis for <jats:italic>MRP1<\/jats:italic> protein. Transfection of lymphocytes with <jats:italic>MRP1<\/jats:italic> gene completely abolished CP\u2010PG (0\u201340\u2009\u03bcM) toxicity. Taken together, these findings suggest that CP\u2010PG accumulation in lymphocytes may be, at least partially, responsible for cancer immunodeficiency. Clinical approaches for overexpressing <jats:italic>MRP1<\/jats:italic>\/GS\u2010X pump in lymphocytes could then play a role as a tool for the management of cancer therapeutics. Copyright \u00a9 2005 John Wiley &amp; Sons, Ltd.<\/jats:p>","DOI":"10.1002\/cbf.1290","type":"journal-article","created":{"date-parts":[[2005,9,19]],"date-time":"2005-09-19T06:46:27Z","timestamp":1127112387000},"page":"23-39","source":"Crossref","is-referenced-by-count":31,"title":["Low expression of <i>MRP1<\/i>\/GS\u2010X pump ATPase in lymphocytes of Walker 256 tumour\u2010bearing rats is associated with cyclopentenone prostaglandin accumulation and cancer immunodeficiency"],"prefix":"10.1002","volume":"24","author":[{"given":"Angela","family":"Kolberg","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tatiana Gomes","family":"Rosa","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Min\u00e9ia Ta\u00edse","family":"Puhl","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gustavo","family":"Scola","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Daiane da Rocha","family":"Janner","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alexandre","family":"Maslinkiewicz","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Denise Jacques","family":"Lagranha","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Thiago Gomes","family":"Heck","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rui","family":"Curi","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"suffix":"Jr.","given":"Paulo Ivo Homem","family":"de Bittencourt","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2005,9,19]]},"reference":[{"key":"e_1_2_1_2_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(68)90010-X"},{"key":"e_1_2_1_3_2","first-page":"45","article-title":"Interactions of vasopressin and prostaglandin E2 in the development of cancer cachexia","volume":"15","author":"Siddiqui RA","year":"1987","journal-title":"Med Sci Res"},{"key":"e_1_2_1_4_2","doi-asserted-by":"publisher","DOI":"10.1016\/0165-2478(84)90073-7"},{"key":"e_1_2_1_5_2","doi-asserted-by":"publisher","DOI":"10.1038\/288597a0"},{"key":"e_1_2_1_6_2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.155.4.1148"},{"key":"e_1_2_1_7_2","doi-asserted-by":"crossref","first-page":"2982","DOI":"10.4049\/jimmunol.143.9.2982","article-title":"The major source of endogenous prostaglandin D2 production is likely antigen\u2010presenting cells: localisation of glutathione\u2010requiring prostaglandin D synthase in histiocytes, dendritic, and Kupffer cells in various rat tissues","volume":"143","author":"Urade Y","year":"1989","journal-title":"J Immunol"},{"key":"e_1_2_1_8_2","doi-asserted-by":"publisher","DOI":"10.1016\/0952-3278(89)90033-1"},{"key":"e_1_2_1_9_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.81.5.1317"},{"key":"e_1_2_1_10_2","doi-asserted-by":"crossref","first-page":"294","DOI":"10.1016\/S0022-3565(25)22326-6","article-title":"Site and mechanism of growth inhibition by prostaglandins\u2014IV: effect of cyclopentenone prostaglandins on cell cycle progression of G1\u2010enriched HeLa S3 cells","volume":"245","author":"Ohno K","year":"1988","journal-title":"J Pharmacol Exp Ther"},{"key":"e_1_2_1_11_2","first-page":"217","article-title":"Interconversion of prostaglandins: a possible signal to control immune system function in cancer","volume":"2","author":"Homem de Bittencourt PI","year":"1992","journal-title":"Cancer Ther Control"},{"key":"e_1_2_1_12_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.86.21.8407"},{"key":"e_1_2_1_13_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0006-2952(99)00299-3"},{"key":"e_1_2_1_14_2","first-page":"1227","article-title":"Glutathione metabolism and glutathione S\u2010conjugate export ATPase (MRP1\/GS\u2010X pump) activity in cancer. I. Differential expression in human cancer cell lines","volume":"45","author":"Homem de Bittencourt PI","year":"1998","journal-title":"Biochem Mol Biol Int"},{"key":"e_1_2_1_15_2","first-page":"1243","article-title":"Glutathione metabolism and glutathione S\u2010conjugate export ATPase (MRP1\/GS\u2010X pump) activity in cancer. II. Cell\u2010to\u2010cell variability, relation with cellular activation state and functional absence of GS\u2010X pump in lymphocytes","volume":"45","author":"Homem de Bittencourt PI","year":"1998","journal-title":"Biochem Mol Biol Int"},{"key":"e_1_2_1_16_2","doi-asserted-by":"publisher","DOI":"10.1007\/BF00493472"},{"key":"e_1_2_1_17_2","first-page":"976","article-title":"Suppressive effects of various antitumor prostaglandin derivatives on the activity levels of DNA polymerases in human cultured tumour cells","volume":"17","author":"Ono K","year":"1987","journal-title":"Adv Prostaglandin Thromboxane Leukotriene Res"},{"key":"e_1_2_1_18_2","doi-asserted-by":"crossref","first-page":"500","DOI":"10.1016\/S0022-3565(25)23605-9","article-title":"Site and mechanism of growth inhibition by prostaglandins. I. Active transport and intracellular accumulation of cyclopentenone prostaglandins, a reaction leading to growth inhibition","volume":"239","author":"Narumiya S","year":"1986","journal-title":"J Pharmacol Exp Ther"},{"key":"e_1_2_1_19_2","doi-asserted-by":"publisher","DOI":"10.1016\/0006-291X(85)91398-1"},{"key":"e_1_2_1_20_2","doi-asserted-by":"publisher","DOI":"10.1038\/47520"},{"key":"e_1_2_1_21_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.94.2.746"},{"key":"e_1_2_1_22_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0006-2952(01)00738-9"},{"key":"e_1_2_1_23_2","doi-asserted-by":"publisher","DOI":"10.1023\/A:1027385513483"},{"key":"e_1_2_1_24_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1349-7006.2004.tb03244.x"},{"key":"e_1_2_1_25_2","doi-asserted-by":"crossref","first-page":"235","DOI":"10.33549\/physiolres.930432","article-title":"ATP\u2010binding cassette (ABC) transporters in human metabolism and diseases","volume":"53","author":"\u0160tefkov\u00e1 J","year":"2004","journal-title":"Physiol Res"},{"key":"e_1_2_1_26_2","first-page":"1879","article-title":"Jackson Roberts L II. Conjugation of 9\u2010deoxy\u2010\u03949,12(E)\u2010prostaglandin D2 with intracellular glutathione and enhancement of its antiproliferative activity by glutathione depletion","volume":"50","author":"Atsmon J","year":"1990","journal-title":"Cancer Res"},{"key":"e_1_2_1_27_2","doi-asserted-by":"publisher","DOI":"10.1016\/0968-0004(92)90489-V"},{"key":"e_1_2_1_28_2","doi-asserted-by":"publisher","DOI":"10.2174\/1389200043489199"},{"key":"e_1_2_1_29_2","doi-asserted-by":"publisher","DOI":"10.1093\/jnci\/92.16.1295"},{"key":"e_1_2_1_30_2","doi-asserted-by":"publisher","DOI":"10.1152\/ajpendo.1990.258.6.E1033"},{"key":"e_1_2_1_31_2","first-page":"1039","article-title":"Effects of aspirin\u2010like drugs on Walker 256 tumour growth and cachexia in rats","volume":"22","author":"Homem de Bittencourt PI","year":"1989","journal-title":"Braz J Med Biol Res"},{"key":"e_1_2_1_32_2","first-page":"631","article-title":"Pyruvate is a lipid precursor for rat lymphocytes in culture: evidence for a lipid exporting capacity","volume":"30","author":"Homem de Bittencourt PI","year":"1993","journal-title":"Biochem Mol Biol Int"},{"volume-title":"Current Protocols in Molecular Biology. Units 1.6 Minipreps of Plasmid DNA, 1.7 Large\u2010Scale Preparation of Plasmid DNA, 1.7.1 Escherichia coli, Plasmids, and Bacteriophages, 1.8 Introduction of Plasmid DNA into Cells","year":"2003","author":"Ausubel FM","key":"e_1_2_1_33_2"},{"key":"e_1_2_1_34_2","first-page":"1255","article-title":"Effects of the antiproliferative cyclopentenone prostaglandin A1 on glutathione metabolism in human cancer cells in culture","volume":"45","author":"Homem de Bittencourt PI","year":"1998","journal-title":"Biochem Mol Biol Int"},{"key":"e_1_2_1_35_2","first-page":"29","volume-title":"Prostaglandins and Related Substances\u2014A Practical Approach","author":"Benedetto C","year":"1987"},{"key":"e_1_2_1_36_2","first-page":"75","volume-title":"Prostaglandins and Related Substances\u2014A Practical Approach","author":"Powell WS","year":"1987"},{"key":"e_1_2_1_37_2","first-page":"53","volume-title":"Prostaglandins and Related Substances\u2014A Practical Approach","author":"Hurst JS","year":"1987"},{"key":"e_1_2_1_38_2","doi-asserted-by":"publisher","DOI":"10.1016\/0003-2697(82)90379-7"},{"key":"e_1_2_1_39_2","doi-asserted-by":"publisher","DOI":"10.1016\/0022-4804(90)90151-Q"},{"key":"e_1_2_1_40_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1432-1033.1982.tb06717.x"},{"key":"e_1_2_1_41_2","doi-asserted-by":"publisher","DOI":"10.1016\/0003-9861(92)90117-F"},{"key":"e_1_2_1_42_2","doi-asserted-by":"publisher","DOI":"10.1016\/0003-2697(76)90527-3"},{"key":"e_1_2_1_43_2","doi-asserted-by":"crossref","first-page":"17343","DOI":"10.1016\/S0021-9258(18)71498-1","article-title":"ATP\/Mg2+\u2010dependent cardiac transport system for glutathione S\u2010conjugates: a study using rat heart sarcolemma vesicles","volume":"264","author":"Ishikawa T","year":"1989","journal-title":"J Biol Chem"},{"key":"e_1_2_1_44_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0076-6879(85)13073-9"},{"key":"e_1_2_1_45_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0076-6879(81)77050-2"},{"key":"e_1_2_1_46_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0076-6879(81)77030-7"},{"key":"e_1_2_1_47_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0076-6879(85)13050-8"},{"key":"e_1_2_1_48_2","doi-asserted-by":"publisher","DOI":"10.1124\/mol.64.1.85"},{"key":"e_1_2_1_49_2","first-page":"3307","article-title":"Location of a protease\u2010hypersensitive region in the multidrug resistance protein (MRP) by mapping of the epitope of MRP\u2010specific monoclonal antibody QCRL\u20101","volume":"56","author":"Hipfner DR","year":"1996","journal-title":"Cancer Res"},{"key":"e_1_2_1_50_2","first-page":"1197","article-title":"Effect of aging on the glutaminase activity of neoplastic and immune tissues","volume":"25","author":"Santos MF","year":"1992","journal-title":"Braz J Med Biol Res"},{"key":"e_1_2_1_51_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0076-6879(81)77050-2"},{"key":"e_1_2_1_52_2","doi-asserted-by":"crossref","first-page":"13382","DOI":"10.1016\/S0021-9258(17)36844-8","article-title":"Functional implications from the effects of 1\u2010chloro\u20102,4\u2010dinitrobenzene and ethacrynic acid on efflux routes for methotrexate and cholate","volume":"269","author":"Henderson GB","year":"1994","journal-title":"J Biol Chem"},{"key":"e_1_2_1_53_2","first-page":"463","article-title":"Evidence that prostaglandins modulate lipogenesis in cultured lymphocytes\u2014a comparison with its effect on macrophages and tumour cells","volume":"33","author":"Homem de Bittencourt PI","year":"1994","journal-title":"Biochem Mol Biol Int"},{"key":"e_1_2_1_54_2","doi-asserted-by":"crossref","first-page":"20366","DOI":"10.1016\/S0021-9258(20)80737-6","article-title":"\u03b3\u2010Glutamylcysteine synthetase and active transport of glutathione S\u2010conjugate are responsive to heat shock in K562 erythroid cells","volume":"268","author":"Kondo T","year":"1993","journal-title":"J Biol Chem"},{"key":"e_1_2_1_55_2","doi-asserted-by":"crossref","first-page":"14981","DOI":"10.1074\/jbc.271.25.14981","article-title":"Coordinated induction of MRP\/GS\u2010X pump and \u03b3\u2010glutamylcysteine synthetase by heavy metals in human leukaemia cells","volume":"271","author":"Ishikawa T","year":"1996","journal-title":"J Biol Chem"}],"container-title":["Cell Biochemistry and Function"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fcbf.1290","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/analyticalsciencejournals.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/cbf.1290","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,9]],"date-time":"2025-10-09T21:57:35Z","timestamp":1760047055000},"score":1,"resource":{"primary":{"URL":"https:\/\/analyticalsciencejournals.onlinelibrary.wiley.com\/doi\/10.1002\/cbf.1290"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2005,9,19]]},"references-count":54,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2006,1]]}},"alternative-id":["10.1002\/cbf.1290"],"URL":"https:\/\/doi.org\/10.1002\/cbf.1290","archive":["Portico"],"relation":{},"ISSN":["0263-6484","1099-0844"],"issn-type":[{"type":"print","value":"0263-6484"},{"type":"electronic","value":"1099-0844"}],"subject":[],"published":{"date-parts":[[2005,9,19]]}}}