Biopolym. Cell. 2008; 24(3):218-224.
http://dx.doi.org/10.7124/bc.0007A3
Structure and Function of Biopolymers
Identification of phosphate transporter NaPi2b as MX35 cancer antigen by modified SEREX approach
1Kiyamova R. G., 1Gryshkova V. S., 2Usenko V. S., 2Khozaenko Y. S., 2Gurtovyy V. A., 3Yin B., 3Ritter G., 3Old L., 4Gout I. T., 1Filonenko V. V.
  1. Institute of Molecular Biology and Genetics, NAS of Ukraine
    150, Akademika Zabolotnoho Str., Kyiv, Ukraine, 03680
  2. Pathomorphological Laboratory "BIONTEK"
    52A/88, Komsomol'ska Str., Dnipropetrovs'k, Ukraine, 49000
  3. Ludwig Institute for Cancer Research, New-York branch at Memorial Sloan-Kettering Cancer Center
    1275 York Avenue, BOX 32 New York, NY 10021-6007, USA
  4. Department of Biochemistry and Molecular Biology,
    University College London
    Gower Str., London WC1E 6BT, UK

Abstract

In this study we describe the identification of sodium-dependent phosphate transporter NaPi2b as MX35 cancer-associated antigen. To achieve this goal we have screened extensively a cDNA expressing library from ovarian cancer cell line OVCAR3 with monoclonal antibody MX35. To further confirm the authenticity of this finding, we showed that bacterially and baculovirally expressed NaPi2b is specifically recognized by MX35 antibody. Moreover, the validity of these results was verified in a parallel study involving affinity purification and mass spectrometry. The epitope for MX35 monoclonal antibody was mapped to the largest extracellular loop of NaPi2b. Taken together, this study uncovers the identity of MX35 antigen and provides molecular tools for studying its function in normal and cancer tissues.
Keywords: MX35 monoclonal antibodies, ovarian cancer, sodium-dependent phosphate cotransporter NaPi2b
Full text: (PDF, in English)

References

[1] Mattes MJ, Look K, Furukawa K, Pierce VK, Old LJ, Lewis JL Jr, Lloyd KO. Mouse monoclonal antibodies to human epithelial differentiation antigens expressed on the surface of ovarian carcinoma ascites cells. Cancer Res. 1987;47(24 Pt 1):6741-50.
[2] Welshinger M, Yin BW, Lloyd KO. Initial immunochemical characterization of MX35 ovarian cancer antigen. Gynecol Oncol. 1997;67(2):188-92.
[3] Finstad CL, Lloyd KO, Federici MG, Divgi C, Venkatraman E, Barakat RR, Finn RD, Larson SM, Hoskins WJ, Humm JL. Distribution of radiolabeled monoclonal antibody MX35 F(ab')2 in tissue samples by storage phosphor screen image analysis: evaluation of antibody localization to micrometastatic disease in epithelial ovarian cancer. Clin Cancer Res. 1997;3(8):1433-42.
[4] Garifulin O. M., Kykot V. O., Gridina N. Y., Kijamova R. G., Gout I. T., Filonenko V. V. Application of SEREX-analysis on colon cancer cases. Exp. Oncol. 2003; 25(2):128–131.
[5] Kyyamova R. G., Rodnin N. V., Garifulin O. M., Tykhonkova I. O., Koroleva E. P., Malets M. S., Gout I. T., Filonenko V. V. Allogenic screening of tumor antigens from thyroid cancer cDNA libraries. Biopolym. Cell. 2004; 20(1-2):151-157.
[6] Scanlan MJ, Chen YT, Williamson B, Gure AO, Stockert E, Gordan JD, T?reci O, Sahin U, Pfreundschuh M, Old LJ. Characterization of human colon cancer antigens recognized by autologous antibodies. Int J Cancer. 1998;76(5):652-8.
[7] Scanlan MJ, Gure AO, Jungbluth AA, Old LJ, Chen YT. Cancer/testis antigens: an expanding family of targets for cancer immunotherapy. Immunol Rev. 2002;188:22-32.
[8] Xu H, Bai L, Collins JF, Ghishan FK. Age-dependent regulation of rat intestinal type IIb sodium-phosphate cotransporter by 1,25-(OH)(2) vitamin D(3). Am J Physiol Cell Physiol. 2002;282(3):C487-93.
[9] Feild JA, Zhang L, Brun KA, Brooks DP, Edwards RM. Cloning and functional characterization of a sodium-dependent phosphate transporter expressed in human lung and small intestine. Biochem Biophys Res Commun. 1999;258(3):578-82.
[10] Eichmuller S, Usener D, Dummer R, Stein A, Thiel D, Schadendorf D. Serological detection of cutaneous T-cell lymphoma-associated antigens. Proc Natl Acad Sci U S A. 2001;98(2):629-34.
[11] Murer H, Forster I, Biber J. The sodium phosphate cotransporter family SLC34. Pflugers Arch. 2004;447(5):763-7.
[12] Yin BW, Kiyamova R, Chua R, Caballero OL, Gout I, Gryshkova V, Bhaskaran N, Souchelnytskyi S, Hellman U, Filonenko V, Jungbluth AA, Odunsi K, Lloyd KO, Old LJ, Ritter G. Monoclonal antibody MX35 detects the membrane transporter NaPi2b (SLC34A2) in human carcinomas. Cancer Immun. 2008;8:3.
[13] Kiyamova R, Gryshkova V, Ovcharenko G, Lituyev D, Malyuchik S, Usenko V, Khozhayenko Y, Gurtovyy V, Yin B, Ritter G, Old L, Filonenko V, Gout I. Development of monoclonal antibodies specific for the human sodium-dependent phosphate co-transporter NaPi2b. Hybridoma (Larchmt). 2008;27(4):277-84.
[14] Traebert M, Hattenhauer O, Murer H, Kaissling B, Biber J. Expression of type II Na-P(i) cotransporter in alveolar type II cells. Am J Physiol. 1999;277(5 Pt 1):L868-73.
[15] Homann V, Rosin-Steiner S, Stratmann T, Arnold WH, Gaengler P, Kinne RK. Sodium-phosphate cotransporter in human salivary glands: molecular evidence for the involvement of NPT2b in acinar phosphate secretion and ductal phosphate reabsorption. Arch Oral Biol. 2005;50(9):759-68.
[16] Xu Y, Yeung CH, Setiawan I, Avram C, Biber J, Wagenfeld A, Lang F, Cooper TG. Sodium-inorganic phosphate cotransporter NaPi-IIb in the epididymis and its potential role in male fertility studied in a transgenic mouse model. Biol Reprod. 2003;69(4):1135-41.
[17] Frei P, Gao B, Hagenbuch B, Mate A, Biber J, Murer H, Meier PJ, Stieger B. Identification and localization of sodium-phosphate cotransporters in hepatocytes and cholangiocytes of rat liver. Am J Physiol Gastrointest Liver Physiol. 2005;288(4):G771-8.
[18] Lundquist P, Murer H, Biber J. Type II Na+-Pi cotransporters in osteoblast mineral formation: regulation by inorganic phosphate. Cell Physiol Biochem. 2007;19(1-4):43-56.
[19] Hattenhauer O, Traebert M, Murer H, Biber J. Regulation of small intestinal Na-P(i) type IIb cotransporter by dietary phosphate intake. Am J Physiol. 1999;277(4 Pt 1):G756-62.
[20] Xu H, Uno JK, Inouye M, Xu L, Drees JB, Collins JF, Ghishan FK. Regulation of intestinal NaPi-IIb cotransporter gene expression by estrogen. Am J Physiol Gastrointest Liver Physiol. 2003;285(6):G1317-24.
[21] Arima K, Hines ER, Kiela PR, Drees JB, Collins JF, Ghishan FK. Glucocorticoid regulation and glycosylation of mouse intestinal type IIb Na-P(i) cotransporter during ontogeny. Am J Physiol Gastrointest Liver Physiol. 2002;283(2):G426-34.
[22] Miyamoto K, Ito M, Kuwahata M, Kato S, Segawa H. Inhibition of intestinal sodium-dependent inorganic phosphate transport by fibroblast growth factor 23. Ther Apher Dial. 2005;9(4):331-5.
[23] Xu H, Collins JF, Bai L, Kiela PR, Ghishan FK. Regulation of the human sodium-phosphate cotransporter NaP(i)-IIb gene promoter by epidermal growth factor. Am J Physiol Cell Physiol. 2001;280(3):C628-36.
[24] Palmada M, Dieter M, Speil A, Bohmer C, Mack AF, Wagner HJ, Klingel K, Kandolf R, Murer H, Biber J, Closs EI, Lang F. Regulation of intestinal phosphate cotransporter NaPi IIb by ubiquitin ligase Nedd4-2 and by serum- and glucocorticoid-dependent kinase 1. Am J Physiol Gastrointest Liver Physiol. 2004;287(1):G143-50.
[25] Shojaiefard M, Lang F. Stimulation of the intestinal phosphate transporter SLC34A2 by the protein kinase mTOR. Biochem Biophys Res Commun. 2006;345(4):1611-4.
[26] Corut A, Senyigit A, Ugur SA, Altin S, Ozcelik U, Calisir H, Yildirim Z, Gocmen A, Tolun A. Mutations in SLC34A2 cause pulmonary alveolar microlithiasis and are possibly associated with testicular microlithiasis. Am J Hum Genet. 2006;79(4):650-6.
[27] Rangel LB, Sherman-Baust CA, Wernyj RP, Schwartz DR, Cho KR, Morin PJ. Characterization of novel human ovarian cancer-specific transcripts (HOSTs) identified by serial analysis of gene expression. Oncogene. 2003;22(46):7225-32.
[28] Jarzab B, Wiench M, Fujarewicz K, Simek K, Jarzab M, Oczko-Wojciechowska M, Wloch J, Czarniecka A, Chmielik E, Lange D, Pawlaczek A, Szpak S, Gubala E, Swierniak A. Gene expression profile of papillary thyroid cancer: sources of variability and diagnostic implications. Cancer Res. 2005;65(4):1587-97.