mRNA expression

Factors determining in vitro survival of human multiple myeloma cells

EXPERIMENTAL STUDIES , , ,

S.S. Shushanov1, T.A. Kravtsova1, and Yu.B. Cherhykh2

1 N.N. Blokhin Russian Cancer Research Center, RAMS, Moscow, Russian Federation

2 M.F. Vladimirskiy Moscow Regional Research-and-Clinical Institute, Moscow, Russian Federation

ABSTRACT

In this work, we investigated the survival of the human MM cell lines, i.e. RPMI1640, RPMI8226, and IM9, depending on the degree of their differentiation and impact of exogenous IGF-1. The study showed that the most and least sensitive to growth factors are IM9 cells with CD138+, CD38–, CD45+, CD56–, or CD19+ immunophenotype and RPMI1640 and RPMI8226 cells with (CD138+, CD38+, CD45–, CD56+/–, or CD19– immunophenotype, respectively The gene expression studies revealed that the level of IGF-1R and IRA mRNA expression was significantly lower in the IM9 cells than in the RPMI1640 or RPMI8226 cells. Also, we established that exogenous IGF-1 could variously influence the survival and growth of MM cells. IGF-1 alone exerts no effect on the myeloma cell viability, but, in combination with serum growth factors, it increases the parameter.

Keywords: multiple myeloma (MM), insulin-like growth factor 1 (IGF-1), cell survival, mRNA expression.

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REFERENCES

  1. Вотякова О.М., Демина Е.А. Множественная миелома. В кн.: Клиниче- ская онкогематология. Руководство для врачей, 2-е изд., перераб и доп. Под ред. М.А. Волковой. М.: Медицина, 2007: 847–73. [Votyakova O.M., Demina Ye.A. Mnozhestvennaya miyeloma. V kn.: Klinicheskaya onkogematologiya. Rukovodstvo dlya vrachey, 2-e izd., pererab i dop. Pod red. M.A. Volkovoy. (Multiple myeloma. In: Clinical oncohematology. Manual for medical practitioners. 2nd ed., rev.&upd. Ed by: M.A. Volkova). M.: Meditsina, 2007: 847–73.]
  2. Jaffe E.E., Harris N., Stein H. et al. World Health Organization Classification of Tumors. Pathology and Genetics of Tumors of Hematopoietic and Lymphoid Tissues. Lyon: IARC Press, 2001: 351.
  3. Raab M.S, Podar K., Breitkreutz I. et al. Multiple myeloma. Lancet 2009; 374: 324–39.
  4. Dispenzieri A., Kyle R.A. Multiple myeloma: clinical features and indications for therapy. Best Pract. Res. Clin. Haematol. 2005; 18: 553–68.
  5. Hideshima T., Bergsagel P.L., Kuehl W.M. et al. Advances in Biology of Multiple Myeloma: Clinical Applications. Blood 2004; 104: 607–18.
  6. Sprynski A.C., Hose D., Caillot L. et al. The role of IGF-1 as a major growth factor for myeloma cell lines and the prognostic relevance of the expression of its receptor. Blood 2009; 113: 4614–26.
  7. Mitsiades C.S., Mitsiades N., Kung A.L. et al. The IGF/IGF-1R system is a major therapeutic target for multiple myeloma, other hematologic malignancies and solid tumors. Blood 2002; 100(11): Abstract 637.
  8. Samani A.A., Yakar S., LeRoith D. et al. The role of the IGF system in cancer growth and metastasis: Overview and recent insights. Endocr. Rev. 2007; 28: 20–47.
  9. Hernandez-Sanchez С., Werner H., Roberts C.T. et al. Differential Regulation of Insulin-like Growth Factor-I (IGF-I) Receptor Gene Expression by IGF-I and Basic Fibroblastic Growth Factor: JBC 1997; 272(8): 4663–70.
  10. Kalitin N., Kostjukova M., Kakpakova E. et al. Vascular endothelial growth factor 1 (VEGFR1) gene expression depends on immunophenotype of human multiple myeloma сells. Eur. J. Cancer 2011; 47(1): S644.
  11. Шушанов С.С., Кравцова Т.А. Цитотоксическое действие доксору- бицина in vitro на клетки множественной миеломы человека. Бюл. экспер. биол. и мед. 2013; 155(2): 195–200. [Shushanov S.S., Kravtsova T.A. Doxorubicine cytotoxic in vitro effect on cells of human multiple myeloma. Byul. eksper. biol. i med. 2013; 155(2): 195–200. (In Russ.)].
  12. Шушанов C.C. Роль инсулиноподобного фактора роста 1 типа (IGF-1) и некоторых других членов системы IGF/инсулин в прогрессии множественной миеломы. Рос. биотер. журн. 2012; 11(3):71–80. [Shushanov C.C. Role of insulin-like growth factor 1 and some other members of IGF/insulin system in progression of multiple myeloma. Ros. bioter. zhurn. 2012; 11(3):71–80. (In Russ.)].
  13. Ludwig T., EggenschwillerJ., Fisher P. et al. Mouse mutants lacking the type 2 IGF receptor (IGF2R) are rescued from perinatal lethality in igf2 and igf-1r null backgrounds. Dev. Biol. 1996; 177: 517–35.
  14. Sacco A., Morcavallo A., Pandini G. et al. Differential signaling activation by insulin and insulin-like growth factors I and II upon binding to insulin receptor isoform A. Endocrinology 2009; 150(8): 3594–602.
  15. Moxham C.P., Duronio V., Jacobs S. et al. Insulin-like growth factor 1 receptor beta–subunit geterogeneity. Evidence for hybrid tetramers composed of insulin-like growth factor 1 and insulin receptor heterodimers. J. Biol. Chem. 1989; 264: 13238–44.
  16. Frasca F., Pandini G., Scalia P. et al. Insulin receptor isoform A a newly recognized, high-affinity insulin-like growth factor II receptor in fetal and cancer cells. Mol. Cell Biol. 1999; 19: 3278–88.
  17. Yamaguchi Y., Flier J.S., Yokoto A. et al. Functional properties of two naturally occurring isoforms of the human insulin receptor in Chinese hamster ovary cells. Endocrinology 1991; 129: 2058–66.
  18. Yu H., Rohan T. Role of insulin-like growth factor family in cancer development and Progression. J. Natl. Cancer Inst. 2000; 92: 1472–89.
  19. Weber J.D., Kuo M.L., Bothner B. et al. Cooperative signals governing ARF mdm2 interaction and nucleolar localization of the complex. Mol. Cell Biol. 2000; 20: 2517–28.
  20. Barton E.R. The ABCs of IGF-1 isoforms: impact of muscle hypertrophy and implications for repair. Appl. Physiol. Nutr. Metab. 2006; 31: 791–7.
  21. Parker A., Cheville J.C., Lohse C. et al. Expression of insulin-like growth factor I receptor and survival in patients with clear cell renal cell carcinoma. J. Urol. 2003; 170: 420–4.
  22. Parker A.S., Cheville J.C., Janney C.A. High expression levels of insulinlike growth factor-I receptor predict poor survival among women with clear-cell renal cell carcinomas. Hum. Pathol. 2002; 33(8): 801–5.
  23. Gicquel C., Bertagna X., Gaston V. et al. Molecular Markers and LongTerm Recurrences in a Large Cohort of Patients with Sporadic Adrenocortical Tumors. Cancer Res. 2001; 61: 6762–67.
  24. Sayer R.A., Lancaster J.M., Pittman J. et al. High insulin-like growth factor-2 (IGF-2) gene expression is an independent predictor of poor survival for patients with advanced stage serous epithelial ovarian cancer. Gynecol. Oncol. 2005; 96(2): 355–61.
  25. Shariat S.F., Kim J., Nguyen C. et al. Correlation of preoperative levels of IGF-I and IGFBP-3 with pathologic parameters and clinical outcome in patients with bladder cancer. Urology 2003; 61(2): 359–64.
  26. Hernandez-Sanchez S., Werner H. et al. Differential regulation of insulinlike growth factor-1 (IGF-1) receptor gene expression by IGF-1 and basic fibroblastic growth factor. Biol. Chem. 1997; 272(8): 4663–70.
  27. Rubini M., Werner H. Gandini E. et al. Platelet-derived growth factor increases the activity of the promotor of the insulin-like growth factor-1 (IGF-1) receptor gene. Exp. Cell Res. 1994; 211(2): 374–9.
  28. Van Riet I., Vande Broek I., Asosingh K. et al. Endothelial cell-tumor cell interactions in multiple myeloma. Hematol. J. 2003; 4(Suppl. 1): P6.3 (abstract).
  29. Vanderkerken K., De Greef C., Asosingh K. et al. Selective initial in vivo homing pattern of 5T2 multiple myeloma cells in the C57BL/KalwRij mouse. Br. J. Cancer 2000; 82: 953–9.
  30. Coppola D., Ferber A., Miura M. et al. A functional insulin-like growth factor 1 receptor is required for the mitogenic and transforming activities of the epidermal growth factor receptor. Mol. Cell Biol. 1994; 14(7): 4588–99.
  31. DeAngelis T., Ferber A., Baserga R. A functional insulin-like growth factor 1 receptor is required for the mitogenic and transforming activities of the platelet derived growth factor receptor. J. Cell Physiol. 1995; 164(1): 214–21.
  32. Ferlin M., Noraz N., Hertogh C. Insulin-like growth factor induces the survival and proliferation of myeloma cells through an interleukin-6-independent transduction pathway. Br. J. Haematol. 2000; 111: 626–4.
  33. Georgii-Hemming P., Wiklund H.J., Ljunggren O. et al. Insulin-like growth factor I is a growth and survival factor in human multiple myeloma cell lines. Blood 1996; 88: 2250–8.
  34. Qiang Y.W., Kopantzev E., Rudikoff S. et al. Insulin like growth factor-I signaling in multiple myeloma: downstream elements, functional correlates, and pathway cross-talk. Blood 2002; 99: 4138–46.