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Effects of TNF Secreting HEK Cells on B Lymphocytes' Apoptosis in Human Chronic Lymphocytic Leukemias

  • Valizadeh, Armita (Department of Anatomy, School of Medicine, Ahvaz Jundishapur University of Medical Sciences) ;
  • Ahmadzadeh, Ahmad (Thalassemia and Hemoglobinopathies Research Center, Shafa Hospital, Ahvaz Jundishapur University of Medical Sciences) ;
  • Teimoori, Ali (Virology Department, Ahvaz Jundishapur University of Medical Sciences) ;
  • Khodadadi, Ali (Cancer, Petroleum and Environmental Pollutants Research Center, Ahvaz Jundishapur University of Medical Sciences) ;
  • Saki, Ghasem (Department of Anatomy, School of Medicine, Ahvaz Jundishapur University of Medical Sciences)
  • Published : 2014.12.18

Abstract

Background: Tumor necrosis factor (TNF) related apoptosis-inducing ligand (TRAIL) is an antitumor candidate in cancer therapy. This study focused on effects of TRAIL, as a proapototic ligand that causes apoptosis, in B-CELL chronic lymphocytic leukemia cells (B-CLL). Materials and Methods: A population of HEK 293 cells was transducted by lentivirus that these achieved ability for producing the TRAIL protein and then HEK 293 cells transducted were placed in the vicinity of CLL cells. After 24 hours of co-culture, apoptosis of CLL cells was assessed by annexin V staining. Results: The amount of Apoptosis was examined separately in four groups: 293 HEK TRAIL ($16.17{\pm}1.04%$); 293 HEK GFP ($2.7{\pm}0.57%$); WT 293 HEK ($2{\pm}2.6%$); and CLL cells ($0.01{\pm}0.01%$). Among the groups studied, the maximum amount of apoptosis was in the group that the vector encoding TRAIL was transducted. In this group, the mean level of soluble TRAIL in the culture medium was 253pg/ml; also flow cytometry analyzes showed that proapotosis in this group was $32.8{\pm}1.6%$, which was higher than the other groups. Conclusions: In this study, we have demonstrated that TNF secreted from HEK 293 cells are effective in death of CLL cells.

Keywords

References

  1. Ashkenazi A, Pai RC, Fong S, et al (1999). Safety and antitumor activity of recombinant soluble Apo2 ligand. J Clin Invest, 104, 155-62. https://doi.org/10.1172/JCI6926
  2. Chen FC, Zhang F, Zhang ZJ, et al (2013). Tumor necrosis factor-$\alpha$ gene polymorphisms and risk of oral cancer: evidence from a meta-analysis. Asian Pac J Cancer Prev, 14, 7243-9. https://doi.org/10.7314/APJCP.2013.14.12.7243
  3. Choi SA, Hwang SK, Wang KC, et al (2011). Therapeutic efficacy and safety of TRAIL producing human adipose tissue - derived mesenchymal stem cells against experimental brainstem glioma. Neuro-Oncol, 13, 61- 9. https://doi.org/10.1093/neuonc/noq147
  4. Duiker EW, Mom CH, de Jong S, et al (2006). The clinical trail of TRAIL. Eur J Cancer, 42, 2233-40. https://doi.org/10.1016/j.ejca.2006.03.018
  5. Grisendi G, Bussolari R, Cafarelli L, et al (2010). Adiposederived mesenchymal stem cells as stable source of tumor necrosis factor-related apoptosis-inducing ligand delivery for cancer therapy. Cancer Res, 70, 3718-29. https://doi.org/10.1158/0008-5472.CAN-09-1865
  6. HengXu, Yan-Na Tian, Bo-Ying Dun, et al (2014). A Novel Monoclonal Antibody Induces Cancer Cell Apoptosis and Enhances the Activity of Chemotherapeutic Drugs. Asian Pac J Cancer Prev, 15, 4423-8. https://doi.org/10.7314/APJCP.2014.15.11.4423
  7. Jiang L, Hao JL, Jin ML,et al (2013). Effect of embelin on TRAIL receptor 2 mAb-induced apoptosis of TRAIL-resistant A549 non-small cell lung cancer cells. Asian Pac J Cancer Prev, 14, 6115-20. https://doi.org/10.7314/APJCP.2013.14.10.6115
  8. Kay NE, Shanafelt TD, Strege AK, et al (2007). Bone biopsy derived marrow stromalelements rescue chronic lymphocytic leukemia B-cells from spontaneous and drug induced celldeath and facilitates an “angiogeneic switch”. Leuk Res, 31, 899-906. https://doi.org/10.1016/j.leukres.2006.11.024
  9. Kim SM, Lim JY, Park SI, et al (2008). Gene therapy using TRAIL-secreting human umbilical cord blood derived mesenchymal stem cells against intracranial glioma. Cancer Res, 68, 9614-23. https://doi.org/10.1158/0008-5472.CAN-08-0451
  10. Lagneaux L, Delforge A, Bron D, et al (1998). Chronic lymphocytic leukemic B cells but not normal B cells are rescued from apoptosis by contact with normal bone marrow stromal cells. Blood, 91, 2387-96.
  11. Loebinger MR, Eddaoudi A, Davies D, et al (2009). Mesenchymal stem cell delivery of TRAIL can eliminate metastatic cancer. Cancer Res, 69, 4134-42.
  12. Mahalingam D, Szegezdi E, Keane M, et al (2009). TRAIL receptor signalling and modulation: Are we on the right TRAIL? Cancer Treat Rev, 35, 280-8. https://doi.org/10.1016/j.ctrv.2008.11.006
  13. Messmer BT, Messmer D, Allen SL, et al (2005). In vivomeasurements document the dynamic cellular kinetics of chronic lymphocytic leukemia B cells. J Clin Invest, 115, 755-64. https://doi.org/10.1172/JCI23409
  14. Montserrat E (2002).Current and developing chemotherapy for CLL. Med Oncol.19, 11-19. https://doi.org/10.1385/MO:19:1:11
  15. Nwabo Kamdje AH, Bassi G, PacelliL, et al (2012). Role of stromal cell-mediated Notch signaling in CLL resistance to chemotherapy. Blood Cancer Journal, 2, 73 https://doi.org/10.1038/bcj.2012.17
  16. Panayiotidis P, Jones D, Ganeshaguru K, et al (1996). Human bone marrow stromal cellsprevent apoptosis and support the survival of chronic lymphocytic leukaemia cells in vitro. Br J Haematol, 92, 97-103. https://doi.org/10.1046/j.1365-2141.1996.00305.x
  17. SeiffertM, SchulzA, Ohl S, et al (2010). Soluble CD14 is a novel monocyte-derived survival factor for chronic lymphocytic leukemia cells, which is induced by CLL cells in vitro and present at abnormally high levels in vivo. Blood, 116, 4223-30. https://doi.org/10.1182/blood-2010-05-284505
  18. Sprick MR, Weigand MA, Rieser E, et al (2000). FADD/MORT1 and caspase-8 are recruited to TRAIL receptors 1 and 2 and are essential for apoptosis mediated by TRAIL receptor 2. Immunity, 12, 599-609. https://doi.org/10.1016/S1074-7613(00)80211-3
  19. Walczak H, Miller RE, Ariail K, et al (1999). Tumoricidal activity of tumor necrosis factor-related apoptosis-inducing ligand In vivo. Nat Med, 5, 157-63. https://doi.org/10.1038/5517
  20. Wiley SR, Schooley K, Smolak PJ, et al (1995). Identification and characterization of a new member of the TNF family that induces apoptosis. Immunity, 3, 673-82. https://doi.org/10.1016/1074-7613(95)90057-8
  21. Zhao B, Li L, Cui K, et al (2011). Mechanisms of TRAIL and gemcitabine induction of pancreatic cancer cell apoptosis. Asian Pac J Cancer Prev, 12, 2675-8.

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