Advances in Molecular OncologyAdvances in Molecular OncologyУспехи молекулярной онкологии2313-805X2413-3787Publishing House ABV Press4410.17650/2313-805X.2015.2.3.43-50REVIEW ARTICLESОБЗОРНЫЕ СТАТЬИTHE NEW DIAGNOSTIC FEATURES OF CD138 (SYNDECAN-1) IN MULTIPLE MYELOMAО НОВЫХ ДИАГНОСТИЧЕСКИХ ВОЗМОЖНОСТЯХ CD138 (СИНДЕКАНА-1) ПРИ МНОЖЕСТВЕННОЙ МИЕЛОМЕKaramyshevaA. F.КарамышеваА. Ф.
Russian Federation

Карамышева Аида Фуадовна

aikaram@yandex.ruResearch Institute of Carcinogenesis, N.N. Blokhin Russian Cancer Research Center, Ministry of Health of Russia, MoscowНаучно-исследовательский институт канцерогенеза ФГБУ «Российский онкологический научный центр имени Н.Н. Блохина» Минздрава России, Москва150920152343501812201518122015Copyright ©; 2015, Karamysheva A.F.Copyright ©; 2015, Карамышева А.Ф.2015Karamysheva A.F.Карамышева А.Ф.https://creativecommons.org/licenses/by/4.0https://umo.abvpress.ru/jour/article/view/44

Syndecan-1 (CD138) is one of the main cell markers used in flow cytometric analysis of multiple myeloma (MM) cells. CD138 and several other markers – CD19, CD45, CD56 – which are often used in order to characterize MM and give the possibility to differentiate MM cells from the normal plasmocytes are described. Only CD138-expressing MM plasma cells are usually taken into account in MM analysis. The current literature data point out that CD138-negative MM plasma cells could be important for MM prognosis, as well. This cell population demonstrates certain properties that are typical to the cancer stem cells. CD138-negative cell population is characterized by higher proliferation, clonogenicity, engraftment in immunodeficient mice as compared to CD138 expressing plasma cells. Besides that, CD138-negative cells were more resistant than CD138-positive cells to the drugs that are used in MM chemotherapy. CD138-negative plasma cells are able to produce CD138 expressing cells upon a long-term culture in vitro and thus to reproduce the heterogenic in CD138 expression population of MM plasma cells. The results of these investigations, as well as statistical data indicating the worse overall survival of CD138 low expressing MM patients point out that CD138-negative population of MM plasma cells should be taken into consideration in MM analysis. Thus, it could be important to find the new markers distinguishing the plasma cell population differing in CD138 expression. Vascular endothelial growth factor receptor VEGFR3 was found to be a new marker with such properties.

multiple myelomaplasma cellsmultiple myeloma markersCD138syndecan-1vascular endothelial growth factor receptorVEGFR3plasma cell populationsprognosisмножественная миеломаплазматические клеткимаркеры множественной миеломыCD138синдекан-1рецептор фактора роста эндотелия сосудов VEGFR3популяции плазмоцитовпрогноз1. Terstappen L.W., Johnsen S., Segers-Nolten I.M., Loken M.R. Identifi- cation and characterization of plasma cells in normal human bone marrow by high- resolution flow cytometry. Blood 1990;76(9):1739–47.Terstappen L.W., Johnsen S., Segers-Nolten I.M., Loken M.R. Identifi- cation and characterization of plasma cells in normal human bone marrow by high- resolution flow cytometry. Blood 1990;76(9):1739–47.2. Вотякова О.М., Демина Е.А. Множественная миелома. В кн.: Клини ческая онкогематология. Под ред. М.А. Волковой. М.: Медицина, 2007. С. 847–73. [Votyakova O.M., Demina E.A. Multiple myeloma. In: Clinical oncohematology. Ed. by M.A. Volkova. Moscow: Meditsina, 2007. Pp. 847–73. (In Russ.)].Вотякова О.М., Демина Е.А. Множественная миелома. В кн.: Клини ческая онкогематология. Под ред. М.А. Волковой. М.: Медицина, 2007. С. 847–73. [Votyakova O.M., Demina E.A. Multiple myeloma. In: Clinical oncohematology. Ed. by M.A. Volkova. Moscow: Meditsina, 2007. Pp. 847–73. (In Russ.)].3. Yaccoby S. The phenotypic plasticity of myeloma plasma cells as expressed by dedifferentiation into an immature, resilient, and apoptosis-resistant phenotype. Clin Cancer Res 2005;11(21):7599–606.Yaccoby S. The phenotypic plasticity of myeloma plasma cells as expressed by dedifferentiation into an immature, resilient, and apoptosis-resistant phenotype. Clin Cancer Res 2005;11(21):7599–606.4. Jego G., Bataille R., Pellat- Deceunynck C. Interleukin-6 is a growth factor for nonmalignant human plasmablasts. Blood 2001;97(6):1817–22.Jego G., Bataille R., Pellat- Deceunynck C. Interleukin-6 is a growth factor for nonmalignant human plasmablasts. Blood 2001;97(6):1817–22.5. Bataille R., Jégo G., Robillard N. et al. The phenotype of normal, reactive and malignant plasma cells. Identification of “many and multiple myelomas” and of new targets for myeloma therapy. Haematologica 2006;91(9):1234–40.Bataille R., Jégo G., Robillard N. et al. The phenotype of normal, reactive and malignant plasma cells. Identification of “many and multiple myelomas” and of new targets for myeloma therapy. Haematologica 2006;91(9):1234–40.6. Harada H., Kawano M.M., Huang N. et al. Phenotypic difference of normal plasma cells from mature myeloma. Blood 1993;81(10):2658–63.Harada H., Kawano M.M., Huang N. et al. Phenotypic difference of normal plasma cells from mature myeloma. Blood 1993;81(10):2658–63.7. Kawano M., Huang N., Harada H. et al. Identification of immature and mature myeloma cells in the bone marrow of human myelomas. Blood 1993;82(2):564–70.Kawano M., Huang N., Harada H. et al. Identification of immature and mature myeloma cells in the bone marrow of human myelomas. Blood 1993;82(2):564–70.8. van Camp B., Durie B.G.M., Spier C. et al. Plasma cells in multiple myeloma express a natural killer cell-associated antigen: CD56 (NKH-1; Leu-19). Blood 1990;76(2):377–82.van Camp B., Durie B.G.M., Spier C. et al. Plasma cells in multiple myeloma express a natural killer cell-associated antigen: CD56 (NKH-1; Leu-19). Blood 1990;76(2):377–82.9. Pellat-Deceunynck C., Bataille R., Robillard N. et al. Expression of CD28 and CD40 in human myeloma cells: a comparative study with normal plasma cells. Blood 1994;84(8):2597–603.Pellat-Deceunynck C., Bataille R., Robillard N. et al. Expression of CD28 and CD40 in human myeloma cells: a comparative study with normal plasma cells. Blood 1994;84(8):2597–603.10. Pellat-Deceunynck C., Barille S., Puthier D. et al. Adhesion molecules on human myeloma cells: Significant changes in expression related to malignancy, tumor spreading, and immortalization. Cancer Res 1995;55(16):3647–53.Pellat-Deceunynck C., Barille S., Puthier D. et al. Adhesion molecules on human myeloma cells: Significant changes in expression related to malignancy, tumor spreading, and immortalization. Cancer Res 1995;55(16):3647–53.11. Robillard N., Pellat-Deceunynck C., Bataille R. Phenotypic characterization of the human myeloma cell growth fraction. Blood 2005;105(12):4845–8.Robillard N., Pellat-Deceunynck C., Bataille R. Phenotypic characterization of the human myeloma cell growth fraction. Blood 2005;105(12):4845–8.12. Moreau P., Robillard N., Avet-Loiseau H. et al. Patients with CD45 negative multiple myeloma receiving high-dose therapy have a shorter survival than those with CD45 positive multiple myeloma. Haematologica 2004;89(5):547–51.Moreau P., Robillard N., Avet-Loiseau H. et al. Patients with CD45 negative multiple myeloma receiving high-dose therapy have a shorter survival than those with CD45 positive multiple myeloma. Haematologica 2004;89(5):547–51.13. Cruz R.D., Tricot G., Zangari M., Zhan F. Progress in myeloma stem cells. Am J Blood Res 2011;1(3):135–45.Cruz R.D., Tricot G., Zangari M., Zhan F. Progress in myeloma stem cells. Am J Blood Res 2011;1(3):135–45.14. Matsui W., Huff C.A., Wang Q. et al. Characterization of clonogenic multiple myeloma cells. Blood 2004; 103(6):2332–6.Matsui W., Huff C.A., Wang Q. et al. Characterization of clonogenic multiple myeloma cells. Blood 2004; 103(6):2332–6.15. Reghunathan R., Bi C., Liu S.C. et al. Clonogenic multiple myeloma cells have shared stemness signature associated with patient survival. Oncotarget 2013;4(8):1230–40.Reghunathan R., Bi C., Liu S.C. et al. Clonogenic multiple myeloma cells have shared stemness signature associated with patient survival. Oncotarget 2013;4(8):1230–40.16. Fuhler G.M., Baanstra M., Chesikc D. et al. Bone marrow stromal cell interaction reduces syndecan-1 expression and induces kinomic changes in myeloma cells. Exp Cell Res 2010;316(11):1816–28.Fuhler G.M., Baanstra M., Chesikc D. et al. Bone marrow stromal cell interaction reduces syndecan-1 expression and induces kinomic changes in myeloma cells. Exp Cell Res 2010;316(11):1816–28.17. Zlei M., Egert S., Wider D. et al. Characterization of in vitro growth of multiple myeloma cells. Exp Hematol 2007;35(10):1550–61.Zlei M., Egert S., Wider D. et al. Characterization of in vitro growth of multiple myeloma cells. Exp Hematol 2007;35(10):1550–61.18. Matsui W., Wang Q., Barber J.P. et al. Clonogenic multiple myeloma progenitors, stem cell properties, and drug resistance. Cancer Res 2008;68(1):190–7.Matsui W., Wang Q., Barber J.P. et al. Clonogenic multiple myeloma progenitors, stem cell properties, and drug resistance. Cancer Res 2008;68(1):190–7.19. Kawano Y., Fujiwara S., Wada N. et al. Multiple myeloma cells expressing low levels of CD138 have an immature phenotype and reduced sensitivity to lenalidomide. Int J Oncol 2012;41(3):876–84.Kawano Y., Fujiwara S., Wada N. et al. Multiple myeloma cells expressing low levels of CD138 have an immature phenotype and reduced sensitivity to lenalidomide. Int J Oncol 2012;41(3):876–84.20. Jourdan M., Ferlin M., Legouffe E. et al. The myeloma cell antigen syndecan-1 is lost by apoptotic myeloma cells. Br J Haematol 1998;100(4):637–46.Jourdan M., Ferlin M., Legouffe E. et al. The myeloma cell antigen syndecan-1 is lost by apoptotic myeloma cells. Br J Haematol 1998;100(4):637–46.21. Christensen J.H., Jensen P.V., Kristensen I.B. et al. Characterization of potential CD138 negative myeloma “stem cells”. Haematologica 2012;97(6):e18–20.Christensen J.H., Jensen P.V., Kristensen I.B. et al. Characterization of potential CD138 negative myeloma “stem cells”. Haematologica 2012;97(6):e18–20.22. Reid S., Yang S., Brown R. et al. Characterisation and relevance of CD138- negative plasma cells in plasma cell myeloma. Int J Lab Hematol 2010;32(6 Pt 1):e190–6.Reid S., Yang S., Brown R. et al. Characterisation and relevance of CD138- negative plasma cells in plasma cell myeloma. Int J Lab Hematol 2010;32(6 Pt 1):e190–6.23. Bayer-Garner I.B., Sanderson R.D., Dhodapkar M.V. et al. Syndecan-1(CD138) immunoreactivity in bone marrow biopsies of multiple myeloma: Shed syndecan-1 accumulates in fibrotic regions. Mod Pathol 2001;14(10):1052–8.Bayer-Garner I.B., Sanderson R.D., Dhodapkar M.V. et al. Syndecan-1(CD138) immunoreactivity in bone marrow biopsies of multiple myeloma: Shed syndecan-1 accumulates in fibrotic regions. Mod Pathol 2001;14(10):1052–8.24. Hosen N. Multiple myeloma-initiating cells. Int J Hematol 2013;97(3):306–12.Hosen N. Multiple myeloma-initiating cells. Int J Hematol 2013;97(3):306–12.25. Vacca A., Ria R., Ribatti D. et al. A paracrine loop in the vascular endothelial growth factor pathway triggers tumor angio- genesis and growth in multiple myeloma. Haematologica 2003;88(2):176–85.Vacca A., Ria R., Ribatti D. et al. A paracrine loop in the vascular endothelial growth factor pathway triggers tumor angio- genesis and growth in multiple myeloma. Haematologica 2003;88(2):176–85.26. Буравцова И.В., Калитин Н.Н., Саблина Ю.А. и др. Экспрессия мРНК генов факторов роста семейства VEGF и их рецепторов у больных множественной миеломой: сопоставление с цитоло гическими характеристиками костного мозга. Российский биотерапевтический журнал 2009;8(4):17–24. [Buravtsova I.V., Kalitin N.N., Sablina Yu.A. et al. Vascular endothelial growth factors and their receptors gene expression in multiple myeloma patients: comparison with the bone marrow cytological characteristics. Rossiyskiy bioterapevticheskiy zhurnal = Russian Biotherapeutic Journal 2009;8(4):17–24. (In Russ.)].Буравцова И.В., Калитин Н.Н., Саблина Ю.А. и др. Экспрессия мРНК генов факторов роста семейства VEGF и их рецепторов у больных множественной миеломой: сопоставление с цитоло гическими характеристиками костного мозга. Российский биотерапевтический журнал 2009;8(4):17–24. [Buravtsova I.V., Kalitin N.N., Sablina Yu.A. et al. Vascular endothelial growth factors and their receptors gene expression in multiple myeloma patients: comparison with the bone marrow cytological characteristics. Rossiyskiy bioterapevticheskiy zhurnal = Russian Biotherapeutic Journal 2009;8(4):17–24. (In Russ.)].27. Buravtsova I.V., Kalitin N.N., Karamysheva A.F., Golenkov A.K. Survival of multiple myeloma patients is different in groups with various intensities of vascular endothelial growth factors(VEGFs) and their receptors (VEGFRs) mRNA co-expression. 36th EORTC-PAMM Winter Meeting, 21–24 January, 2015, Marseille, France. P. 106.Buravtsova I.V., Kalitin N.N., Karamysheva A.F., Golenkov A.K. Survival of multiple myeloma patients is different in groups with various intensities of vascular endothelial growth factors(VEGFs) and their receptors (VEGFRs) mRNA co-expression. 36th EORTC-PAMM Winter Meeting, 21–24 January, 2015, Marseille, France. P. 106.28. Kostjukova M.N., Karamysheva A.F. CD138+ and CD138– multiple myeloma cells demonstrate different membrane expression of interleukin-6 receptor(CD126) and vascular endothelial growth factor receptor 3 (VEGFR3). Иммунология гемопоэза = Haematopoiesis Immunology 2014;12(1–2):96.Kostjukova M.N., Karamysheva A.F. CD138+ and CD138– multiple myeloma cells demonstrate different membrane expression of interleukin-6 receptor(CD126) and vascular endothelial growth factor receptor 3 (VEGFR3). Иммунология гемопоэза = Haematopoiesis Immunology 2014;12(1–2):96.29. Буравцова И.В., Костюкова М.Н., Калитин Н.Н. и др. Экспрессия маркера плазматических клеток CD138 и рецептора факторов роста эндотелия сосудов VEGFR3 у больных множественной миеломой: корреляция с прогнозом. Иммунология гемопоэза 2015;13(1):120. [Buravtsova I.V., Kostyukova M.N., Kalitin N.N. et al. Expression of the marker of plasma cells CD138 and vascular endothelial growth factor receptor VEGFR3 in patients with multiple myeloma: correlation with prognosis. Immunologiya gemopoeza = Haematopoiesis Immunology 2015;13(1):120. (In Russ.)].Буравцова И.В., Костюкова М.Н., Калитин Н.Н. и др. Экспрессия маркера плазматических клеток CD138 и рецептора факторов роста эндотелия сосудов VEGFR3 у больных множественной миеломой: корреляция с прогнозом. Иммунология гемопоэза 2015;13(1):120. [Buravtsova I.V., Kostyukova M.N., Kalitin N.N. et al. Expression of the marker of plasma cells CD138 and vascular endothelial growth factor receptor VEGFR3 in patients with multiple myeloma: correlation with prognosis. Immunologiya gemopoeza = Haematopoiesis Immunology 2015;13(1):120. (In Russ.)].30. Stanley M.J., Leibersbach B.F., Liu W. et al. Heparan sulfate-mediated cell aggregation. Syndecans-1 and -4 mediate intercellular adhesion following their transfection into human B lymphoid cells. J Biol Chem 1995;270(10):5077–83.Stanley M.J., Leibersbach B.F., Liu W. et al. Heparan sulfate-mediated cell aggregation. Syndecans-1 and -4 mediate intercellular adhesion following their transfection into human B lymphoid cells. J Biol Chem 1995;270(10):5077–83.31. Ridley R.C., Xiao H., Hata H. et al. Expression of syndecan regulates human myeloma plasma cell adhesion to type I collagen. Blood 1993;81(3):767–74.Ridley R.C., Xiao H., Hata H. et al. Expression of syndecan regulates human myeloma plasma cell adhesion to type I collagen. Blood 1993;81(3):767–74.32. Liebersbach B.F., Sanderson R.D. Expression of syndecan-1 inhibits cell invasion into type-I collagen. J Biol Chem 1994;269(31):20013–9.Liebersbach B.F., Sanderson R.D. Expression of syndecan-1 inhibits cell invasion into type-I collagen. J Biol Chem 1994;269(31):20013–9.33. Dhodapkar M.V., Abe E., Theus A. et al. Syndecan-1 is a multifunctional regulator of myeloma pathobiology; control of tumor survival, growth, and bone cell differentiation. Blood 1998;91(8):2679–88.Dhodapkar M.V., Abe E., Theus A. et al. Syndecan-1 is a multifunctional regulator of myeloma pathobiology; control of tumor survival, growth, and bone cell differentiation. Blood 1998;91(8):2679–88.34. Seidel C., Sundan A., Hjorth M. et al. Serum syndecan-1: a new independent prognostic marker in multiple myeloma. Blood 2000;95(2):388–92.Seidel C., Sundan A., Hjorth M. et al. Serum syndecan-1: a new independent prognostic marker in multiple myeloma. Blood 2000;95(2):388–92.