Study of the development of chemoresistance in melanoma cell lines using proteome analysis
Corresponding Author
Pranav Sinha
Institut für medizinische und chemische Labordiagnostik, Landeskrankenhaus Klagenfurt, Klagenfurt, Austria
Institut für Medizinische und Chemische Labordiagnostik, Landeskrankenhaus Klagenfurt, St. Veiter Straße 47, A-9020 Klagenfurt, Austria Fax: +43-463-43823039===Search for more papers by this authorJulia Poland
Institut für Laboratoriumsmedizin und Pathobiochemie, Universitätsklinikum Charité, Berlin, Germany
Search for more papers by this authorSandro Kohl
Institut für Laboratoriumsmedizin und Pathobiochemie, Universitätsklinikum Charité, Berlin, Germany
Search for more papers by this authorMartina Schnölzer
Zentrale Proteinanalytik, DKFZ, Heidelberg, Germany
Search for more papers by this authorHeike Helmbach
Klinische Kooperationseinheit für Dermatoonkologie (DKFZ), Abteilung für Dermatologie, Universitätsklinikum Mannheim Mannheim, Germany
Search for more papers by this authorGero Hütter
Medizinische Klinik III, Hämatologie, Onkologie und Transfusionsmedizin, Universitätsklinikum Benjamin Franklin, Berlin, Germany
Search for more papers by this authorHermann Lage
Institut für Pathologie, Universitätsklinikum Charité, Berlin, Germany
Search for more papers by this authorDirk Schadendorf
Klinische Kooperationseinheit für Dermatoonkologie (DKFZ), Abteilung für Dermatologie, Universitätsklinikum Mannheim Mannheim, Germany
Search for more papers by this authorCorresponding Author
Pranav Sinha
Institut für medizinische und chemische Labordiagnostik, Landeskrankenhaus Klagenfurt, Klagenfurt, Austria
Institut für Medizinische und Chemische Labordiagnostik, Landeskrankenhaus Klagenfurt, St. Veiter Straße 47, A-9020 Klagenfurt, Austria Fax: +43-463-43823039===Search for more papers by this authorJulia Poland
Institut für Laboratoriumsmedizin und Pathobiochemie, Universitätsklinikum Charité, Berlin, Germany
Search for more papers by this authorSandro Kohl
Institut für Laboratoriumsmedizin und Pathobiochemie, Universitätsklinikum Charité, Berlin, Germany
Search for more papers by this authorMartina Schnölzer
Zentrale Proteinanalytik, DKFZ, Heidelberg, Germany
Search for more papers by this authorHeike Helmbach
Klinische Kooperationseinheit für Dermatoonkologie (DKFZ), Abteilung für Dermatologie, Universitätsklinikum Mannheim Mannheim, Germany
Search for more papers by this authorGero Hütter
Medizinische Klinik III, Hämatologie, Onkologie und Transfusionsmedizin, Universitätsklinikum Benjamin Franklin, Berlin, Germany
Search for more papers by this authorHermann Lage
Institut für Pathologie, Universitätsklinikum Charité, Berlin, Germany
Search for more papers by this authorDirk Schadendorf
Klinische Kooperationseinheit für Dermatoonkologie (DKFZ), Abteilung für Dermatologie, Universitätsklinikum Mannheim Mannheim, Germany
Search for more papers by this authorAbstract
Malignant melanomas have poor prognosis since treatment with anti-neoplastic agents is mostly ineffective. The biological mechanisms of this strong intrinsic therapy resistance are unknown. In order to identify new molecular factors potentially associated with the drug-resistant phenotype of malignant melanoma, a panel of human melanoma cell variants exhibiting low and high levels of resistance to four commonly used anticancer drugs in melanoma treatment, i.e., vindesine, etoposide, cisplatin, and fotemustine, was characterized using proteomic tools (two-dimensional electrophoresis for protein fractionation and matrix assisted laser desorption/ionization-time of flight (MALDI-TOF)-mass spectrometry for protein identification). In the neutral and weak acidic milieu (pH 4.0–8.0) a total number of 14 proteins showed alterations in expression whereas 20 proteins were differentially expressed in the basic milieu (pH 8.0–11.0). Besides proteins with unknown physiologic function, several factors were identified that show chaperone activity. Moreover, proteins involved in drug detoxification, metabolism, and regulation of apoptotic pathways could be identified. The possible role of these proteins in the development of chemoresistance is discussed, although detailed functional tests with these proteins have still to be performed. Nevertheless, it is clear that this proteomic approach for studying chemoresistance phenomena is a prerequisite before further investigation can yield insight into the biology and development of drug resistance in malignant melanoma.
REFERENCES
- 1 McGovern, V. J., Pathology of Melanoma: An overview, J. B. Lippincott, Philadelphia 1985, pp. 29–42.
- 2 Marsoni, S., Hoth, D., Simon, R., Leyland Jones, B., de Rosa, M., Wittes, R. E., Cancer Treat. Rep. 1987, 71, 71–80.
- 3 Ho, V. C., Sober, A. J., J. Am. Acad. Dermatol. 1990, 22, 159–176.
- 4 Algermissen, B., Bauer, F., Schadendorf, D., Kropp, J. D., Czarnetzki, B. M., Exp. Dermatol. 1994, 3, 290–297.
- 5 Kern, M. A., Helmbach, H., Artuk, M., Karmann, D., Jurgowsky, K., Schadendorf, D., Anticancer Res. 1997, 17, 4359–4370.
- 6 Lage, H., Christmann, M., Kern, M. A., Dietel, M., Pick, M., Keina, B., Schadendorf, D., Int. J. Cancer 1999, 80, 744–750.
10.1002/(SICI)1097-0215(19990301)80:5<744::AID-IJC19>3.0.CO;2-5 CASPubMedWeb of Science®Google Scholar
- 7 Christmann, M., Pick, M., Lage, H., Schadendorf, D., Kaina, B., Int. J. Cancer 2001, 92, 123–129.
- 8 Nessling, M., Kern, M. A., Schadendorf, D., Lichter, P., Cytogenet. Cell Genet. 1999, 87, 286–290.
- 9 Lage, H., Helmbach, H., Dietel, M., Schadendorf, D., Br. J. Cancer 2000, 82, 488–491.
- 10 Grottke, C., Mantwill, K., Dietel, M., Schadendorf, D., Lage, H., Int. J. Cancer 2000, 88, 535–546.
- 11 Lage, H., Helmbach, H., Grottke, C., Dietel, M., Schadendorf, D., FEBS Lett. 2001, 494, 54–59.
- 12 Sinha, P., Kohl, S., Fischer, J., Hütter, G., Kern, M., Köttgen, E., Dietel, M., Lage, H., Schnölzer, M., Schadendorf, D., Electrophoresis 2000, 21, 3048–3057.
10.1002/1522-2683(20000801)21:14<3048::AID-ELPS3048>3.0.CO;2-W CASPubMedWeb of Science®Google Scholar
- 13 Rabilloud, T., Valette, C., Lawrence, J. J., Electrophoresis 1994, 15, 1552–1558.
- 14 Cheung, C. K., Mak, Y. T., Swaminathan, R., Ann. Clin. Biochem. 1987, 24, 140–144.
- 15 Altland, K., Altland, A., Clin. Chem. 1984, 30, 2098–2103.
- 16 Hochstrasser, D. F., Patchornik, A., Merril, C. R., Anal. Biochem. 1988, 173, 412–423.
- 17 Görg, A., Boguth, G., Obermaier, C., Posch, A., Weiss, W., Electrophoresis 1995, 16, 1079–1086.
- 18 Görg, A., Postel, W., Günther, S., Electrophoresis 1988, 9, 531–546.
- 19 Laemmli, U. K., Nature 1970, 227, 680–685.
- 20 Neuhoff, V., Arold, N., Taube, D., Ehrhardt, W., Electrophoresis 1988, 9, 255–262.
- 21 Neuhoff, V., Stamm, R., Pardowitz, I., Arold, N., Ehrhardt, W., Taube, D., Electrophoresis 1990, 11, 101–117.
- 22 Celis, J. E., Ratz, G., Basse, B., B., L. J., Celis, A., Jensen, N. A., Groimov, P., High-Resolution Two-Dimensional Gel Electrophoresis of Proteins: Isoelectric Focusing (IEF) and Nonequilibrium pH Gradient Electrophoresis (NEPHGE), Academic Press, San Diego, CA 1998, pp. 375–385.
- 23 Poland, J., Sinha, P., Siegert, A., Schnolzer, M., Korf, U., Hauptmann, S., Electrophoresis 2002, 23, 1174–1184.
10.1002/1522-2683(200204)23:7/8<1174::AID-ELPS1174>3.0.CO;2-O CASPubMedWeb of Science®Google Scholar
- 24 Jensen, O. N., Podtelejnikov, A., Mann, M., Rapid Commun. Mass Spectrom. 1996, 10, 1371–1378.
10.1002/(SICI)1097-0231(199608)10:11<1371::AID-RCM682>3.0.CO;2-5 CASPubMedWeb of Science®Google Scholar
- 25 Helmbach, H., Rossmann, E., Kern, M. A., Schadendorf, D., Int. J. Cancer 2001, 93, 617–622.
- 26 Sinha, P., Hütter, G., Köttgen, E., Dietel, M., Schadendorf, D., Lage, H., J. Biochem. Biophys. Methods 1998, 37, 105–116.
- 27 Sinha, P., Hütter, G., Köttgen, E., Dietel, M., Schadendorf, D., Lage, H., Electrophoresis 1999, 20, 2952–2960.
10.1002/(SICI)1522-2683(19991001)20:14<2952::AID-ELPS2952>3.0.CO;2-H CASPubMedWeb of Science®Google Scholar
- 28 Sinha, P., Hütter, G., Kotzgen, E., Dietel, M., Schadendorf, D., Lage, H., Electrophoresis 1999, 20, 2952–2960.
10.1002/(SICI)1522-2683(19991001)20:14<2952::AID-ELPS2952>3.0.CO;2-H CASPubMedWeb of Science®Google Scholar
- 29 Sinha, P., Hütter, G., Köttgen, E., Dietel, M., Schadendorf, D., Lage, H., Electrophoresis 1999, 20, 2961–2969.
10.1002/(SICI)1522-2683(19991001)20:14<2961::AID-ELPS2961>3.0.CO;2-L CASPubMedWeb of Science®Google Scholar
- 30 Sinha, P., Poland, J., Schnölzer, M., Celis, J. E., Lage, H., Electrophoresis 2001, 22, 2990–3000.
- 31 Sarto, C., Binz, P. A., Mocarelli, P., Electrophoresis 2000, 21, 1218–1226.
10.1002/(SICI)1522-2683(20000401)21:6<1218::AID-ELPS1218>3.0.CO;2-H CASPubMedWeb of Science®Google Scholar
- 32 Creagh, E. M., Sheehan, D., Cotter, T. G., Leukemia 2000, 14, 1161–1173.
- 33 Arrigo, A. P., Biol. Chem. 1998, 379, 19–26.
- 34 Mehlen, P., Schulze-Osthoff, K., Arrigo, A. P., J. Biol. Chem. 1996, 271, 16510–16514.
- 35 van den Dobbelsteen, D. J., Nobel, C. S., Schlegel, J., Cotgreave, I. A., Orrenius, S., Slater, A. F., J. Biol. Chem. 1996, 271, 15420–15427.
- 36 Garrido, C., Bruey, J. M., Fromentin, A., Hammann, A., Arrigo, A. P., Solary, E., FASEB J. 1999, 13, 2061–2070.
- 37 Creagh, E. M., Cotter, T. G., Immunology 1999, 97, 36–44.
- 38 Takayama, S., Bimston, D. N., Matsuzawa, S., Freeman, B. C., Aime-Sempe, C., Xie, Z., Morimoto, R. I., Reed, J. C., EMBO J. 1997, 16, 4887–4896.
- 39 Kudo, H., Hirayoshi, K., Kitagawa, Y., Imamura, S., Nagata, K., Exp. Cell. Res. 1994, 212, 219–224.
- 40 Jain, N., Brickenden, A., Ball, E. H., Sanwal, B. D., Arch. Biochem. Biophys. 1994, 314, 23–30.
- 41 Nakai, A., Satoh, M., Hirayoshi, K., Nagata, K., J. Cell. Biol. 1992, 117, 903–914.
- 42 Thomson, C. A., Ananthanarayanan, V. S., Biochem. J. 2000, 349, 877–883.
- 43 Ikegawa, S., Nakamura, Y., Gene 1997, 194, 301–303.
- 44 Buchner, J., Trends Biochem. Sci. 1999, 24, 136–141.
- 45 Pearl, L. H., Prodromou, C., Curr. Opin. Struct. Biol. 2000, 10, 46–51.
- 46 Srivastava, P. K., Udono, H., Blachere, N. E., Li, Z., Immunogenetics 1994, 39, 93–98.
- 47 Galea-Lauri, J., Richardson, A. J., Latchman, D. S., Katz, D. R., J. Immunol. 1996, 157, 4109–4118.
- 48 Schadendorf, D., Jurgovsky, K., Kohlmus, C. M., Czarnetzki, B. M., J. Invest. Dermatol. 1995, 105, 109–112.
- 49 Schadendorf, D., Makki, A., Stahr, C., van Dyck, A., Wanner, R., Scheffer, G. L., Flens, M. J., Scheper, R., Henz, B. M., Am. J. Pathol. 1995, 147, 1545–1552.
- 50 Krishna, R., Mayer, L. D., Eur. J. Pharm. Sci. 2000, 11, 265–283.
- 51 Moscow, J. A., Dixon, K. H., Cytotechnology 1993, 12, 155–170.
- 52 Nielsen, D., Maare, C., Skovsgaard, T., Gen. Pharmacol. 1996, 27, 251–255.
- 53 Stavrovskaya, A. A., Biochemistry (Mosc) 2000, 65, 95–106.
- 54 van der Kolk, D. M., Vellenga, E., Müller, M., de Vries, E. G., Adv. Exp. Med. Biol. 1999, 457, 187–198.
- 55 Chung, Y. M., Yoo, Y. D., Park, J. K., Kim, Y. T., Kim, H. J., Anticancer Res. 2001, 21, 1129–1133.
- 56 Ueno, M., Masutani, H., Arai, R. J., Yamauchi, A., Hirota, K., Sakai, T., Inamoto, T., Yamaoka, Y., Yodoi, J., Nikaido, T., J. Biol. Chem. 1999, 274, 35809–35815.
- 57 Park, S. H., Chung, Y. M., Lee, Y. S., Kim, H. J., Kim, J. S., Chae, H. Z., Yoo, Y. D., Clin. Cancer Res. 2000, 6, 4915–4920.
- 58 Spataro, V., Toda, T., Craig, R., Seeger, M., Dubiel, W., Harris, A. L., Norbury, C., J. Biol. Chem. 1997, 272, 30470–30475.
- 59 Dou, Q. P., McGuire, T. F., Peng, Y., An, B., J. Pharmacol. Exp. Ther. 1999, 289, 781–790.
- 60 Ogiso, Y., Tomida, A., Lei, S., Omura, S., Tsuruo, T., Cancer Res. 2000, 60, 2429–2434.
- 61 Hideshima, T., Richardson, P., Chauhan, D., Palombella, V. J., Elliott, P. J., Adams, J., Anderson, K. C., Cancer Res. 2001, 61, 3071–3076.
- 62 Markert, J. M., Fuller, C. M., Gillespie, G. Y., Bubien, J. K., McLean, L. A., Hong, R. L., Lee, K., Gullans, S. R., Mapstone, T. B., Benos, D. J., Physiol. Genomics 2001, 5, 21–33.
- 63 Borer, R. A., Lehner, C. F., Eppenberger, H. M., Nigg, E. A., Cell 1989, 56, 379–390.
- 64 Szebeni, A., Olson, M. O., Prot. Sci 1999, 8, 905–912.
- 65 Zatsepina, O. V., Bouniol-Baly, C., Amirand, C., Debey, P., Dev. Biol. 2000, 223, 354–370.
