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Vault-related resistance to anticancer drugs determined by the expression of the major vault protein LRP

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Abstract

In this review we analyze the data supporting the notion that vault-related MDR, as reflected by LRP/MVP overexpression, represents a marker of drug resistance in vitro and in the clinic. Vaults, besides playing a fundamental biological role, may be involved in a novel mechanism of MDR.

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References

  • Biedler JL (1994) Drug resistance: genotype versus phenotype. Cancer Res, 666-678.

  • Chugani DC, Kedersha NL, Rome LH (1991) Vault immunofluorescence in the brain: New insights regarding the origin of microglia. J Neurosci 11: 256-268.

    CAS  Google Scholar 

  • Chugani DC, Rome LH, Kedersha NL (1993) Evidence that vault ribonucleoprotein particles localize to the nuclear pore complex. J Cell Sci 106: 23-29.

    CAS  Google Scholar 

  • Coley HM, Amos WB, Twentyman PR, Workman P (1993) Examination by laser scanning confocal fluorescence imaging microscopy of the subcellular localisation of anthracyclines in parent and multidrug resistant cell lines. Br J Cancer 67: 1316-1323.

    CAS  Google Scholar 

  • Den Boer ML, Zwaan CM, Pieters R, Kazemier KM, Rottier MMA, Flens MJ, Scheper RJ, Veerman AJP (1997) Optimal immunocytochemical and flow cytometric detection of P-gp, MRP, and LRP in childhood acute lymphoblastic leukaemia. Leukaemia 11: 1078-1085.

    Article  CAS  Google Scholar 

  • Dietel M, Arps H, Lage H, Niendorf A (1990) Membrane vesicle formation due to acquired mitoxantrone resistance in human gastric carcinoma cell line EPG85-257. Cancer Research 50: 6100-6106.

    CAS  Google Scholar 

  • Dingemans AMC, van Ark-Otte J, van der Valk P, Apolinario RM, Scheper RJ, Postmus PE, Giaccone G (1996) Expression of the human major vault protein LRP in human lung cancer samples and normal lung tissue. Ann Oncol 7: 625-630.

    CAS  Google Scholar 

  • Filipits M, Pohl G, Stranzl T, Suchomel RW, Scheper RJ, Jäger U, Geissler K, Lechner K and Pirker R (1998) Expression of the Lung Resistance Protein (LRP) predicts poor outcome in de novo acute myeoloid leukemia. Blood 91: 1508-1513.

    CAS  Google Scholar 

  • Flens MJ, Izquierdo MA, Scheffer GL, Fritz JM, Meijer CJLM, Scheper RJ, Zaman GJR (1994) Immunochemical detection of the multidrug resistance-associated protein MRP in human multidrug-resistant tumour cells by monoclonal antibodies. Cancer Res 54: 4557-4563.

    CAS  Google Scholar 

  • Flens MJ, Zaman GJR, van der Valk P, Izquierdo MA, Schroeijers AB, Scheffer GL, van der Groep P, de Haas M, Meijer CJLM, Scheper RJ (1996) Tissue distribution of the multidrug resistance protein. Am J Pathol 148: 1237-1247.

    CAS  Google Scholar 

  • Flens MJ, Scheffer GL, van der Valk P, Broxterman HJ, Eijdems EWHM, Huysmans ACLM, Izquierdo MA, Scheper RJ (1997) Identification of novel drug resistance-associated proteins by a panel of rat monoclonal antibodies. Int J Cancer, in press.

  • Futscher BW, Abbaszadegan MR, Domann F, Dalton WS (1994) Analysis of MRP MRNA in mitoxantrone-selected, multidrug-resistant human tumour cells. Biochem Pharmacol 47: 1601-1606.

    Article  CAS  Google Scholar 

  • Garbe C (1993) Chemotherapy and chemoimmunotherapy in disseminated malignant melanoma. Melanoma Res 3: 291-299.

    CAS  Google Scholar 

  • Gervasoni JE Jr, Fields SZ, Krishna S, Baker MA, Rosado M, Thuraisamy K, Hindenburg AA, Taub RN (1991) Subcellular distribution of daunorubicin in P-glycoprotein-positive and-negative drug-resistantcell lines using laser-assisted confocal microscopy. Cancer Research 51: 4955-4963.

    CAS  Google Scholar 

  • Goldstein LJ, Pastan I, Gottesman MM (1992) Multidrug resistance in human cancer. (Review). Critical Reviews in Oncology-Hematology 12: 243-253.

    Article  CAS  Google Scholar 

  • Hart SM, Ganeshaguru K, Scheper RJ, Hoffbrand AV, Mehta AB (1995) Expression of the human major vault protein in haematological malignancies. Amer Soc Haematol Dec, (Abstract).

  • Herrmann C, Volknandt W, Wittich B, Kellner R, Zimmermann H (1996) The major vault protein (MVP100) is contained in cholinergic nerve terminals of electric ray organ. J Biol Chem 271: 13908-13915.

    Article  CAS  Google Scholar 

  • Higgins CF (1992) ABC Transporters - From Microorganisms to Man. Annu Rev Cell Biol 8: 67-113.

    Article  CAS  Google Scholar 

  • Hindenburg AA, Gervasoni JE, Jr., Krishna S, Stewart VJ, Rosado M, Lutzky J, Bhalla K, Baker MA, Taub RN (1989) Intracellular distribution and pharmacokinetics of daunorubicin in anthracycline-sensitive and-resistant HL-60 cells. Cancer Research 49: 4607-4614.

    CAS  Google Scholar 

  • Ikeda K, Oka M, Narasaki F, Nakano R, Fukuda M, Mizuta Y, Yamada Y, Kamihira K, Tomonaga M, Kohno S (1997) LRPm gene expression in human gastric cancers, and adult T-cell leukaemia cells. Procc Am Ass Cancer Res 390 (abst. 2616).

    Google Scholar 

  • Izquierdo MA, van der Zee AGJ, Vermorken JB, van der Valk P, Belien JAM, Giaccone G, Scheffer GL, Flens MJ, Pinedo HM, Kenemans P, Meijer CJLM, de Vries EGE, Scheper RJ (1995) Drug resistance-associated marker LRP for prediction of response to chemotherapy and prognoses in advanced ovarian carcinoma. J Nat Cancer Inst 87: 1230-1237.

    CAS  Google Scholar 

  • Izquierdo MA, Scheffer GL, Flens MJ, Giaccone G, Broxterman HJ, Meijer CJLM, van der Valk P, Scheper RJ (1996a) Broad distribution of the multidrug resistance-related vault lung resistance protein in normal human tissues and tumours. Am J Pathol 148: 877-887.

    CAS  Google Scholar 

  • Izquierdo MA, Shoemaker RH, Flens MJ, Scheffer GL, Wu L, Prather TR, Scheper RJ (1996b) Overlapping phenotypes of multidrug resistance among panels of human cancer-cell lines. Int J Cancer 65: 230-237.

    Article  CAS  Google Scholar 

  • Izquierdo MA, Scheffer GL, Flens MJ, Schroeijers AB, van der Valk P, Scheper RJ (1996c) Major vault protein LRP-related multidrug resistance. Eur J Cancer 32A: 979-984.

    Article  CAS  Google Scholar 

  • Kedersha NL and Rome LH (1986) Isolation and characterization of a novel ribonucleoprotein particle:large structures contain a single species of small RNA. J Cell Biol 103: 699-709.

    Article  CAS  Google Scholar 

  • Kedersha NL, Miquel M-C, Bittner D, Rome LH (1990) Vaults II. Ribonucleoprotein structures are highly conserved among higher and lower eukaryotes. J Cell Biol 110: 895-901.

    Article  CAS  Google Scholar 

  • Kedersha NL, Heuser JE, Chugani DC, Rome LH (1991) Vaults III. Vault ribonucleoprotein particles open into flower-like structures with octagonal symmetry. J Cell Biol 112: 225-235.

    Article  CAS  Google Scholar 

  • Kedersha NL, Rome LH(1993) CDNA cloning and disruption of the major vault protein alpha (mvpA) in Dictyostelium discoideum. J Biol Chem 268: 15356-15360.

    Google Scholar 

  • Kickhoefer VA, Searles RP, Kedersha NL, Garber ME, Johnson DL, Rome LH (1993) Vault ribonucleoprotein particles from rat and bullfrog contain related small RNA that is transcribed by RNA polymerase III. J Biol Chem 268: 7868-7873.

    CAS  Google Scholar 

  • Kickhoefer VA, Rome LH (1994) The sequence of a CDNA encoding the major vault protein from Rattus norvegicus.Gene 151: 257-260.

    Article  CAS  Google Scholar 

  • Kickhoefer VA, Rajavel KS, Scheffer GL, Dalton WS, Scheper RJ, Rome LH (1998) Vaults are up-regulated in multidrug resistant cancer cell lines. J Biol Chem 273: 8971-8974.

    Article  CAS  Google Scholar 

  • Klumper E, de Boer ML, Pieters R, Huismans DR, Rottier MMA, Zwaan MC, Scheffer GL, Scheper RJ, Veerman AJP (1995) Non-P-glycoprotein mediated resistance to anthracyclines is associated with the expression of a 110 Kd protein in relapsed childhood acute lymphoblastic leukaemia. In: Klumper E. Thesis. VU University Press, pp. 117-130.

  • Komarov P, Shtil A, Buckingman L, Roninson I, Coon J (1997) Genes encoding for different drug resistance-associated proteins (MDR1, LRP, and MRP) are differentially regulated by extracellular stimuli. Procc Am Ass Cancer Res 479 (abst. 3207).

    Google Scholar 

  • Kuiper CM, Broxterman HJ, Baas F, Schuurhuis GJ, Haisma HJ, Scheffer GL, Lankelma J, Pinedo HM (1990) Drug transport variants without P-glycoprotein overexpression from a human squamous lung cancer cell line after selection with doxorubicin. J Cell Pharmacol 1: 35-41.

    CAS  Google Scholar 

  • Laurencot CM, Scheffer GL, Scheper RJ, Shoemaker RH (1997) Increased LRP MRNA expression is associated with the MDR phenotype in intrinsically resistant human cancer cell lines. Int J Cancer 72: 1-6.

    Article  Google Scholar 

  • List AF, Spier CS, Grogan TM, Johnson C, Roe DJ, Greer JP, Wolff SN, Broxterman HJ, Scheffer GL, Scheper RJ, Dalton WS (1996) Overexpression of the major vault transporter protein Lung Resistance Protein predicts treatment outcome in acute myeloid leukaemia. Blood 87: 2464-2469.

    CAS  Google Scholar 

  • Loe DW, Deeley RG, Cole SPC (1996) Biology of the multidrug resistance-associated protein, MRP. Eur J Cancer 32A: 945-957.

    Article  CAS  Google Scholar 

  • Moran E, Clearly I, Larkin AM, Amhlaoibh RN, Masterson A, Scheper RJ, Izquierdo MA, Center M, O'Sullivan F, Clynes M (1997) Co-expression of MDR-associated markers, including P-170, MRP and LRP and cytoskeletal proteins, in three resistant variants of the human ovarian carcinoma cell line, OAW42. Eur J Cancer 33: 652-660.

    Article  CAS  Google Scholar 

  • Michieli M, Damiani D, Ermacora A, Raspadori D, Michelutti A, Grimaz S, Fanin R, Russo D, Lauria F, Masolini P, Baccarani M (1997) P-glycoprotein (PGP) and lung resistance-related protein (LRP) expression and function in leukaemic blast cells. Br J Haematol 96: 356-365.

    Article  CAS  Google Scholar 

  • Parker R, Mechetner E, Garcia R, Pavich D, Fruehauf J (1997) Acquired cisplatin resistance in human ovarian cancer A2780/CP70 cells is associated with MRP and LRP over-expression. Procc Am Ass Cancer Res 481 (abst. 3219).

    Google Scholar 

  • Pieters R, Klumper E, Kaspers GJL, Veerman AJP (1997) Everything you always wanted to know about cellular drug resistance in childhood acute lymphoblastic leukaemia. Crit Rev Oncol Hematol 25: 11-26.

    CAS  Google Scholar 

  • Ramani P, Dewchand H (1995) Expression of mdr1/P-glycoprotein and p110 in neuroblastoma. J Pathol 175: 13-22.

    Article  CAS  Google Scholar 

  • Rome LH, Kedersha NL, Chugani DC (1991) Unlocking vaults: organelles in search of a function. Trends Cell Biol 1: 47-50.

    Article  CAS  Google Scholar 

  • Schadendorf D, Herfordt R, Czarnetzki BM (1995a) P-glycoprotein expression in primary and metastatic malignant melanoma. Br J Dermatol 132: 551-555.

    Article  CAS  Google Scholar 

  • Schadendorf D, Makki A, Stahr C, van Dyck A, Wanner R, Scheffer GL, Flens MJ, Scheper RJ, Henz BM (1995b) Membrane transport proteins associated with drug resistance expressed in human melanoma. Am J Pathol 147: 1545-1552.

    CAS  Google Scholar 

  • Scheffer GL, Wijngaard PLJ, Flens MJ, Izquierdo MA, Slovak ML, Pinedo HM, Meijer CJLM, Clevers HC, Scheper RJ (1995) The drug resistance-related protein LRP is the human major vault protein. Nature Med 1: 578-582.

    Article  CAS  Google Scholar 

  • Scheper RJ, Broxterman HJ, Scheffer GL, Kaaijk P, Dalton WS, van Heijningen THM, van Kalken CK, Slovak ML, Devries EGE, van der Valk P, Meijer CJLM, Pinedo HM (1993) Overexpression of a M(r) 110,000 Vesicular Protein in Non-P-Glycoprotein-Mediated Multidrug Resistance. Cancer Res 53: 1475-1479.

    CAS  Google Scholar 

  • Schroeijers AB, Scheffer GL, Flens MJ, Meijer GA, van der Valk P, Scheper RJ (1998) Immunohistochemical detection of the human major vault protein LRP with two monoclonal antibodies LRP-56 and LMR-5 in formalin-fixed, paraffin-embedded tissues. Am J Pathol 152: 373-378.

    CAS  Google Scholar 

  • Schuurhuis GJ, Broxterman HJ, Cervantes A, van Heijningen TH, de Lange JH, Baak JP, Pinedo HM, Lankelma J (1989) Quantitative determination of factors contributing to doxorubicin resistance in multidrug-resistant cells. Journal of the National Cancer Institute 81: 1887-1892.

    CAS  Google Scholar 

  • Shao Y, De Giuli R, Wyler B, Lehnert M (1995) Overexpression of MDR1/P-glycoprotein and MRP but not LRP is mutually exclusive in multidrug resistant human myeloma cells selected with doxorubicin. Proc Am Ass Cancer Res 36: 337 (abst 2006).

    Google Scholar 

  • Slovak ML, Ho JP, Cole SPC, Deeley RG, Greenberger L, de Vries EGE, Broxterman HJ, Scheffer GL, Scheper RJ (1995) The LRP gene encoding a major vault protein associated with drug resistance maps proximal to MRP on chromosome 16: evidence that chromosome breakage plays a key role in MRP or LRP gene amplification. Cancer Res 55: 4214-4219.

    CAS  Google Scholar 

  • Stein U, Walther W, CM, Scheffer GL, Scheper RJ, Shoemaker RH (1997) Tumour necrosis factor-α and expression of the multidrug resistance-associated genes LRPand MRP. J Natl Cancer Inst 89: 807-813.

    Article  CAS  Google Scholar 

  • Sugawara I, Akiyama S, Scheper RJ, Itoyama S (1997) Lung resistance protein (LRP) expression in human normal tissues in comparison with that of MDR1 and MRP. Cancer Let 112: 23-31.

    Article  CAS  Google Scholar 

  • van der Valk P, van Kalken CK, Ketelars H, Broxterman HJ, Scheffer GL, Kuiper CM, Tsuruo T, Lankelma J, Meijer CJLM, Pinedo HM, Scheper RJ (1990) Distribution of multi-drug resistance-associated P-glycoprotein in normal and neoplastic human tissues. Ann Oncol 1: 56-64.

    CAS  Google Scholar 

  • Vasu SK, Rome LH (1995) Dictyostelium vaults: Disruption of the major proteins reveals growth and morphological defects and uncovers a new associated protein. J Biol Chem 270: 16588-16594.

    Article  CAS  Google Scholar 

  • Veerman AJP, den Boer ML, Pieters R, Kazemier KM, Rottier MMA, Kaspers GJL, Scheper RJ, Janka G, Henze G, Creutzig U (1997) Intracellular daunorubicin concentrations and LRP are related to drug resistance in childhood leukaemia. Procc Am Ass Cancer Res 422 (abst. 2958).

    Google Scholar 

  • Verovski VN, van der Berge DL, Delvaeye MM, Scheper RJ, De Neve WJ, Storme GA (1996) Low-level doxorubicin resistance in P-glycoprotein-negative human pancreatic tumour PSN1/ADR cells implicates a brefeldin A-sensitive mechanism of drug extrusion. Br J Cancer 73: 596-602.

    CAS  Google Scholar 

  • Versantvoort CHM, Withoff S, Broxterman HJ, Kuiper CM, Scheper RJ, Mulder NH, Devries EGE (1995) Resistance-associated factors in human small-cell lung-carcinoma GLC(4) sub-lines with increasing adriamycin resistance. Int J Cancer 61: 375-380.

    CAS  Google Scholar 

  • Wyler B, Shao Y, Schneider E, Cianfriglia M, Scheper RJ, Frey BM, Gieseler F, Schmid L, Twentyman P, Lehnert M (1997) Intermittent exposure to doxorubicin in vitroselects for multifactorial non-P-glycoprotein-associated multidrug resistance in RPMI 8226 human myeloid cells. Br J Haematol 97: 65-75.

    Article  CAS  Google Scholar 

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Authors and Affiliations

  1. Department of Medical Oncology, Catalan Institute of Oncology, Av. Casteldefels Km 2.7, 08907 Hospitalet de LI., Barcelona, Spain

    Miguel A. Izquierdo

  2. Department of Pathology, Free University Hospital, De Boelelaan 1117, 1081 HV, Amsterdam, The Netherlands

    George L. Scheffer, Anouk B. Schroeijers, Mariska C. de Jong & Rik J. Scheper

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  1. Miguel A. Izquierdo
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  2. George L. Scheffer
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  3. Anouk B. Schroeijers
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  4. Mariska C. de Jong
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  5. Rik J. Scheper
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Izquierdo, M.A., Scheffer, G.L., Schroeijers, A.B. et al. Vault-related resistance to anticancer drugs determined by the expression of the major vault protein LRP. Cytotechnology 27, 137–148 (1998). https://doi.org/10.1023/A:1008004502861

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