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01-05-2015 | Research Article

Proapoptotic CD95L levels in normal human serum and sera of breast cancer patients

Authors: Vicente Olimón-Andalón, Adriana Aguilar-Lemarroy, Sarah Ratkovich-González, Aida Uribe-López, Ignacio Mariscal-Ramírez, Raúl Delgadillo-Cristerna, Pablo Ortiz-Lazareno, Georgina Hernández-Flores, Ruth de Celis, Alejandro Bravo-Cuellar, Luis F. Jave-Suárez

Published in: Tumor Biology | Issue 5/2015

Abstract

The CD95 pathway is a critical apoptotic pathway used by immune cells to avoid cancer development. CD95 ligand (CD95L) is found in several forms, as a cell membrane-associated form, a soluble metalloprotease-cleaved form, and a soluble but membrane-bound CD95L released on cell-derived exosomes. In this study, we used a cell-based assay to evaluate the activity of proapoptotic CD95L in sera from healthy individuals and breast cancer patients. We confirmed that our cell-based assay using Jurkat cells was sensitive to the presence of proapoptotic CD95L in serum, and apoptosis induction by mechanisms other than CD95 was discriminated using apoptosis-resistant Jurkat subclones. Our results indicated a proapoptotic potential of normal serum that involved CD95L. Sera from breast cancer patients exhibited significantly decreased apoptosis induction, due to increased CD95 receptor levels compared with healthy women. Apoptotic potential tended to decrease as the Breast Imaging Reporting and Data System grade increased, and we observed restoration of proapoptotic potential after tumor removal. The CD95L in serum responsible for apoptotic induction was associated with high-molecular-weight particles, perhaps with exosomes. The sera of healthy individuals generally contain a proapoptotic environment, and this property is mainly maintained by the presence of CD95L. Furthermore, measurement of CD95L-mediated apoptosis induction by sera could be a useful parameter to be evaluated during cancer development and therapeutic response.

Hengartner MO. The biochemistry of apoptosis. Nature. 2000;407(6805):770–6. doi:10.1038/35037710.CrossRefPubMed

Birkeland SA, Storm HH, Lamm LU, Barlow L, Blohme I, Forsberg B, et al. Cancer risk after renal transplantation in the Nordic countries, 1964-1986. Int J Cancer. 1995;60(2):183–9.CrossRefPubMed

Vajdic CM, McDonald SP, McCredie MR, van Leeuwen MT, Stewart JH, Law M, et al. Cancer incidence before and after kidney transplantation. JAMA. 2006;296(23):2823–31.CrossRefPubMed

Bonnet F, Chene G. Evolving epidemiology of malignancies in HIV. Curr Opin Oncol. 2008;20(5):534–40. doi:10.1097/CCO.0b013e32830a5080.CrossRefPubMed

Lavrik I, Golks A, Krammer PH. Death receptor signaling. J Cell Sci. 2005;118(Pt 2):265–7. doi:10.1242/jcs.01610.CrossRefPubMed

Leithauser F, Dhein J, Mechtersheimer G, Koretz K, Bruderlein S, Henne C, et al. Constitutive and induced expression of APO-1, a new member of the nerve growth factor/tumor necrosis factor receptor superfamily, in normal and neoplastic cells. Lab Investig. 1993;69(4):415–29.PubMed

Keane MM, Ettenberg SA, Lowrey GA, Russell EK, Lipkowitz S. Fas expression and function in normal and malignant breast cell lines. Cancer Res. 1996;56(20):4791–8.PubMed

Gupta S, Su H, Bi R, Agrawal S, Gollapudi S. Life and death of lymphocytes: a role in immunesenescence. Immun Ageing. 2005;2:12. doi:10.1186/1742-4933-2-12.CrossRefPubMedPubMedCentral

Martinez-Lorenzo MJ, Anel A, Gamen S, Monle NI, Lasierra P, Larrad L. Activated human T cells release bioactive Fas ligand and APO2 ligand in microvesicles. J Immunol. 1999;163(3):1274–81.PubMed

10.

Monleon I, Martinez-Lorenzo MJ, Monteagudo L, Lasierra P, Taules M, Iturralde M, et al. Differential secretion of Fas ligand- or APO2 ligand/TNF-related apoptosis-inducing ligand-carrying microvesicles during activation-induced death of human T cells. J Immunol. 2001;167(12):6736–44.CrossRefPubMed

11.

Kim JW, Wieckowski E, Taylor DD, Reichert TE, Watkins S, Whiteside TL. Fas ligand-positive membranous vesicles isolated from sera of patients with oral cancer induce apoptosis of activated T lymphocytes. Clin Cancer Res: Off J Am Assoc Cancer Res. 2005;11(3):1010–20.

12.

Penna A, Khadra N, Tauzin S, Vacher P, Legembre P. The CD95 signaling pathway: to not die and fly. Commun Integr Biol. 2012;5(2):190–2. doi:10.4161/cib.18888.CrossRefPubMedPubMedCentral

13.

Lu L, Qian S, Hershberger PA, Rudert WA, Lynch DH, Thomson AW. Fas ligand (CD95L) and B7 expression on dendritic cells provide counter-regulatory signals for T cell survival and proliferation. J Immunol. 1997;158(12):5676–84.PubMed

14.

Hamann KJ, Dorscheid DR, Ko FD, Conforti AE, Sperling AI, Rabe KF, et al. Expression of Fas (CD95) and FasL (CD95L) in human airway epithelium. Am J Respir Cell Mol Biol. 1998;19(4):537–42. doi:10.1165/ajrcmb.19.4.3100.CrossRefPubMed

15.

Walczak H. Death receptor-ligand systems in cancer, cell death, and inflammation. Cold Spring Harbor Perspect Biol. 2013;5(5):a008698. doi:10.1101/cshperspect.a008698.CrossRef

16.

Tanaka M, Suda T, Haze K, Nakamura N, Sato K, Kimura F, et al. Fas ligand in human serum. Nat Med. 1996;2(3):317–22.CrossRefPubMed

17.

Gillis S, Watson J. Biochemical and biological characterization of lymphocyte regulatory molecules. V. Identification of an interleukin 2-producing human leukemia T cell line. J Exp Med. 1980;152(6):1709–19.CrossRefPubMed

18.

Weis M, Schlegel J, Kass GE, Holmstrom TH, Peters I, Eriksson J, et al. Cellular events in Fas/APO-1-mediated apoptosis in JURKAT T lymphocytes. Exp Cell Res. 1995;219(2):699–708. doi:10.1006/excr.1995.1281.CrossRefPubMed

19.

Martinez-Lorenzo MJ, Alava MA, Anel A, Pineiro A, Naval J. Release of preformed Fas ligand in soluble form is the major factor for activation-induced death of Jurkat T cells. Immunology. 1996;89(4):511–7.CrossRefPubMedPubMedCentral

20.

Peter ME, Dhein J, Ehret A, Hellbardt S, Walczak H, Moldenhauer G, et al. APO-1 (CD95)-dependent and -independent antigen receptor-induced apoptosis in human T and B cell lines. Int Immunol. 1995;7(11):1873–7.CrossRefPubMed

21.

Juo P, Woo MS, Kuo CJ, Signorelli P, Biemann HP, Hannun YA, et al. FADD is required for multiple signaling events downstream of the receptor Fas. Cell Growth Diff: Molec Biol J Am Assoc Cancer Res. 1999;10(12):797–804.

22.

Juo P, Kuo CJ, Yuan J, Blenis J. Essential requirement for caspase-8/FLICE in the initiation of the Fas-induced apoptotic cascade. Curr Biol: CB. 1998;8(18):1001–8.CrossRefPubMed

23.

Sedgwick E. The breast ultrasound lexicon: breast imaging reporting and data system (BI-RADS). Semin Roentgenol. 2011;46(4):245–51. doi:10.1053/j.ro.2011.04.001.CrossRefPubMed

24.

Sheen-Chen SM, Chen HS, Eng HL, Chen WJ. Circulating soluble Fas in patients with breast cancer. World J Surg. 2003;27(1):10–3. doi:10.1007/s00268-002-6378-5.CrossRefPubMed

25.

Hewala TI, Abd El-Monaim NA, Anwar M, Ebied SA. The clinical significance of serum soluble Fas and p53 protein in breast cancer patients: comparison with serum CA 15-3. Pathol Oncol Res. 2012;18(4):841–8. doi:10.1007/s12253-012-9512-1.CrossRefPubMed

26.

Kato K, Ohshima K, Ishihara S, Anzai K, Suzumiya J, Kikuchi M. Elevated serum soluble Fas ligand in natural killer cell proliferative disorders. Br J Haematol. 1998;103(4):1164–6.CrossRefPubMed

27.

Mizutani Y, Hongo F, Sato N, Ogawa O, Yoshida O, Miki T. Significance of serum soluble Fas ligand in patients with bladder carcinoma. Cancer. 2001;92(2):28–93.CrossRef

28.

Mizutani Y, Hongo F, Sato N, Ogawa O, Yoshida O, Miki T. Significance of serum soluble Fas ligand in patients with bladder carcinoma. Cancer. 2001;45(3):199–204.

29.

Malleter M, Tauzin S, Bessede A, Castellano R, Goubard A, Godey F, et al. CD95L cell surface cleavage triggers a prometastatic signaling pathway in triple-negative breast cancer. Cancer Res. 2013;73(22):6711–21. doi:10.1158/0008-5472.CAN-13-1794.CrossRefPubMed

30.

Koncz G, Hancz A, Chakrabandhu K, Gogolak P, Kerekes K, Rajnavolgyi E, et al. Vesicles released by activated T cells induce both Fas-mediated RIP-dependent apoptotic and Fas-independent nonapoptotic cell deaths. J Immunol. 2012;189(6):2815–23. doi:10.4049/jimmunol.1102827.CrossRefPubMed

31.

Barnhart BC, Legembre P, Pietras E, Bubici C, Franzoso G, Peter ME. CD95 ligand induces motility and invasiveness of apoptosis-resistant tumor cells. EMBO J. 2004;23(15):3175–85. doi:10.1038/sj.emboj.7600325.CrossRefPubMedPubMedCentral

32.

Chen L, Park SM, Tumanov AV, Hau A, Sawada K, Feig C, et al. CD95 promotes tumour growth. Nature. 2010;465(7297):492–6. doi:10.1038/nature09075.CrossRefPubMedPubMedCentral

33.

LA OR, Tai L, Lee L, Kruse EA, Grabow S, Fairlie WD, et al. Membrane-bound Fas ligand only is essential for Fas-induced apoptosis. Nature. 2009;461(7264):659–63. doi:10.1038/nature08402.CrossRef

34.

Kern P, Dietrich M, Hemmer C, Wellinghausen N. Increased levels of soluble Fas ligand in serum in Plasmodium falciparum malaria. Infect Immun. 2000;68(5):3061–3.CrossRefPubMedPubMedCentral

35.

Sugita S, Taguchi C, Takase H, Sagawa K, Sueda J, Fukushi K, et al. Soluble Fas ligand and soluble Fas in ocular fluid of patients with uveitis. Br J Ophthalmol. 2000;84(10):1130–4.CrossRefPubMedPubMedCentral

36.

Abe R, Shimizu T, Shibaki A, Nakamura H, Watanabe H, Shimizu H. Toxic epidermal necrolysis and Stevens-Johnson syndrome are induced by soluble Fas ligand. Am J Pathol. 2003;162(5):1515–20. doi:10.1016/S0002-9440(10)64284-8.CrossRefPubMedPubMedCentral

37.

Holm AM, Tjonnfjord G, Yndestad A, Beiske K, Muller F, Aukrust P, et al. Polyclonal expansion of large granular lymphocytes in common variable immunodeficiency - association with neutropenia. Clin Exp Immunol. 2006;144(3):418–24. doi:10.1111/j.1365-2249.2006.03086.x.CrossRefPubMedPubMedCentral

38.

Nabipour I, Kalantarhormozi M, Assadi M, Jafari SM, Gharibi M, Ahmadi E, et al. Influence of levothyroxine treatment on serum levels of soluble Fas (CD95) and Fas Ligand (CD95L) in chronic autoimmune hypothyroidism. Endocrine. 2010;38(3):406–11. doi:10.1007/s12020-010-9401-x.CrossRefPubMed

39.

Paunel-Gorgulu A, Flohe S, Scholz M, Windolf J, Logters T. Increased serum soluble Fas after major trauma is associated with delayed neutrophil apoptosis and development of sepsis. Crit Care. 2011;15(1):R20. doi:10.1186/cc9965.CrossRefPubMedPubMedCentral

40.

D’Agostino S, Salamone M, Di Liegro I, Vittorelli ML. Membrane vesicles shed by oligodendroglioma cells induce neuronal apoptosis. Int J Oncol. 2006;29(5):1075–85.PubMed

41.

Bergmann C, Strauss L, Wieckowski E, Czystowska M, Albers A, Wang Y, et al. Tumor-derived microvesicles in sera of patients with head and neck cancer and their role in tumor progression. Head Neck. 2009;31(3):371–80. doi:10.1002/hed.20968.CrossRefPubMedPubMedCentral

42.

Arbuckle E, Langlois NE, Eremin O, Heys SD. Evidence for Fas counter attack in vivo from a study of colorectal cancer. Oncol Rep. 2000;7(1):45–7.PubMed

43.

Debatin KM. CD95 system counter attack and prognostic impact. Onkologie. 2006;29(8-9):358–9. doi:10.1159/000094698.PubMed

44.

Hefler L, Mayerhofer K, Nardi A, Reinthaller A, Kainz C, Tempfer C. Serum soluble Fas levels in ovarian cancer. Obstet Gynecol. 2000;96(1):65–9.PubMed

45.

Furuya Y, Nagakawa O, Fuse H. Prognostic significance of serum soluble Fas level and its change during regression and progression of advanced prostate cancer. Endocr J. 2003;50(5):629–33.CrossRefPubMed

46.

Abbasova SG, Vysotskii MM, Ovchinnikova LK, Obusheva MN, Digaeva MA, Britvin TA, et al. Cancer and soluble FAS. Bull Exp Biol Med. 2009;148(4):638–42.CrossRefPubMed

47.

Aguilar-Lemarroy A, Romero-Ramos JE, Olimon-Andalon V, Hernandez-Flores G, Lerma-Diaz JM, Ortiz-Lazareno PC, et al. Apoptosis induction in Jurkat cells and sCD95 levels in women’s sera are related with the risk of developing cervical cancer. BMC Cancer. 2008;8:99. doi:10.1186/1471-2407-8-99.CrossRefPubMedPubMedCentral

Title: Proapoptotic CD95L levels in normal human serum and sera of breast cancer patients
Authors: Vicente Olimón-Andalón
Adriana Aguilar-Lemarroy
Sarah Ratkovich-González
Aida Uribe-López
Ignacio Mariscal-Ramírez
Raúl Delgadillo-Cristerna
Pablo Ortiz-Lazareno
Georgina Hernández-Flores
Ruth de Celis
Alejandro Bravo-Cuellar
Luis F. Jave-Suárez
Publication date: 01-05-2015
Publisher: Springer Netherlands
Published in: Tumor Biology / Issue 5/2015
Print ISSN: 1010-4283
Electronic ISSN: 1423-0380
DOI: https://doi.org/10.1007/s13277-014-3005-7

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