DOI QR코드

DOI QR Code

Effects of FasL Expression in Oral Squamous Cell Cancer

  • Fang, Li (Stomatologic Hospital and College, Anhui Medical University, Key Lab. of Oral Diseases Research of Anhui Province) ;
  • Sun, Lin (Stomatologic Hospital and College, Anhui Medical University, Key Lab. of Oral Diseases Research of Anhui Province) ;
  • Hu, Fang-Fang (Stomatologic Hospital and College, Anhui Medical University, Key Lab. of Oral Diseases Research of Anhui Province) ;
  • Chen, Qiao-Er (Stomatologic Hospital and College, Anhui Medical University, Key Lab. of Oral Diseases Research of Anhui Province)
  • Published : 2013.01.31

Abstract

Purpose: To probe the role of FasL in cell apoptosis in oral squamous cell carcinomas (OSCCs). Methods: The expression of Fas/FasL was assessed in 10 cases of normal oral epithelium, 38 cases of OSCC and tumor infiltrating lymphocytes (TIL), and 11 cases of metastatic lymph nodes by immunohistochemistry. Apoptosis of tumor cells and TIL was detected by terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling assay (TUNEL). FasL-induction of T cell apoptosis was tested by co-culture assay in vitro with SCC-9 and Jurkat T cells. Results: The 10 cases of normal oral epithelium all demonstrated extensive expression of Fas, the positive rate being largely down-regulated in OSCC (21/38) (P<0.05) compared to the normal (10/10). At the same time, the positive rate of FasL significantly increased in OSCC (P<0.05) especially those with lymph node metastasis (P<0.05). The positive rates of Fas in well and middle differentiated OSCC were higher than those in poor differentiated OSCC (P<0.05). The AI of tumor cells in Fas-positive OSCC was remarkably higher than that in Fas-negative OSCC (P<0.01), with a positive correlation between Fas expression and cell differentiation as well as apoptosis (r=0.68, P<0.01). The AI of tumor cells in FasL positive OSCC was remarkably lower than that in control while the AI of TIL was higher than in FasL negative OSCC (P<0.05). The AI of tumor cells reversely correlated with that of TIL (r = -0. 72, P<0.05). It was found that SCC-9 cells expressing functional FasL could induce apoptosis of Jurkat cells as demonstrated by co-culture assays. As a conclusion, it is evident that OSCC cells expressing FasL can induce apoptosis in Fas-expressing T cells. Conclusions: In progression of OSCC, expression of the Fas/FasL changes significantly. The results suggest that FasL is a mediator of immune privilege in OSCC and may serve as an marker for predicting malignant change in oral tissues.

Keywords

References

  1. Bennett MW, O'connell J, O'sullivan GC, et al (1999). Expression of Fas ligand by human gastric adenocarcinomas: a potential mechanism of immune escape in stomach cancer. Gut, 44, 156-62. https://doi.org/10.1136/gut.44.2.156
  2. Bozdogan N, Bozdogan O, Pak I, et al (2010). Fas, Fas ligand, tumor infiltrating lymphocytes, and macrophages in malignant melanoma: an immunohistochemical study. Int J Dermato, 149, 761-7
  3. Cai Z, Yang F, Yu L, et al (2012). Activated T cell exosomes promote tumor invasion via Fas signaling pathway. J Immunol, 188, 5954-61. https://doi.org/10.4049/jimmunol.1103466
  4. Chen Q, Samaranayake LP, Zhen X, et al (1999). Up-regulation of Fas ligand and down-regulation of Fas expression in oral carcinogenesis. Oral Oncol, 35, 548-53 https://doi.org/10.1016/S1368-8375(99)00029-9
  5. de Camargo Cancela M, Voti L, Guerra-Yi M, et al (2010). Oral cavity cancer in developed and in developing countries: population-based incidence. Head Neck, 32, 357-67
  6. Ehrenschwender M, Wajant H (2009). The role of FasL and Fas in health and disease. Adv Exp Med Biol, 647, 64-93 https://doi.org/10.1007/978-0-387-89520-8_5
  7. Gomes TS, Oshima CT, Segreto HR, et al (2011). The extrinsic apoptotic signaling pathway in gastric adenocarcinomas assessed by tissue microarray. Pathol Res Pract, 207, 613-7. https://doi.org/10.1016/j.prp.2011.06.010
  8. Gryko M, Guzinska-Ustymowicz K, Pryczynicz A, et al (2011). Correlation between Fas and FasL proteins expression in normal gastric mucosa and gastric cancer. Folia Histochem Cytobiol, 49, 142-7 https://doi.org/10.5603/FHC.2011.0020
  9. Hadzi-Mihailovic M, Raybaud H, Monteil R, et al (2009). Expression of Fas/FasL in patients with oral lichen planus. J Buon, 14, 487-93
  10. Hub H (1997). Fas-mediated apoptosis in tumor formation and defense. Biol Chem, 378, 1405-12.
  11. Hueber A, Welsandt G, Jordan JF, et al (2002). Characterization of CD95 ligand(CD95L) induced apoptosis in human tenon fibroblasts. Exp Eye Res, 75, 1-8. https://doi.org/10.1006/exer.2001.1171
  12. Ibrahim R, Frederickson H, Parr A, et al (2006). Expression of FasL in squamous cell carcinomas of the cervix and cervical intraepithelial neoplasia and its role in tumor escape mechanism. Cancer, 106, 1065-77. https://doi.org/10.1002/cncr.21697
  13. Ji J, Wernli M, Buechner S, et al (2003). Fas ligand downregulation with antisense oligonucleotides in cells and in cultured tissues of normal skin epidermis and basal cell carcinoma. J Invest Dermatol, 120, 1094-9. https://doi.org/10.1038/jid.2003.13
  14. Kassouf N, MH (2008). Oral cancer cell lines can use multiple ligands, including Fas-L, TRAIL and TNF-alpha, to induce apoptosis in Jurkat T cells: possible mechanisms for immune escape by head and neck cancers. Oral Oncol, 44, 672-82. https://doi.org/10.1016/j.oraloncology.2007.08.013
  15. Koornstra JJ, de Jong S, Boersma-van Eck W, et al (2009). Fas ligand expression in lynch syndrome-associated colorectal tumours. Pathol Oncol Res, 15, 399-406. https://doi.org/10.1007/s12253-008-9136-7
  16. Kurita H, Nakanishi Y, Nishizawa R, et al (2010). Impact of different surgical margin conditions on local recurrence of oral squamous cell carcinoma. Oral Oncol, 46, 814-7. https://doi.org/10.1016/j.oraloncology.2010.08.014
  17. Nagata S, Golstein P (1995). The Fas death factor. Science, 267, 1449-56. https://doi.org/10.1126/science.7533326
  18. Narayana N, Gist J, Smith T, et al (2010). Desmosomal component expression in normal, dysplastic and oral squamous cell carcinoma. Dermatol Res Pract, 2010, 649731.
  19. Shimonishi T, Isse K, Shibata F, et al (2000). Up-regulation of fas ligand at early stages and down-regulation of Fas at progressed stages of intrahepatic cholangiocarcinoma reflect evasion from immune surveillance. Hepatology, 32, 761-69. https://doi.org/10.1053/jhep.2000.18192
  20. Tian J, Pan F, Li J, et al (2012). Association between the FAS/FASL polymorphisms and gastric cancer risk: a metaanalysis. Asian Pac J Cancer Prev, 13, 945-51. https://doi.org/10.7314/APJCP.2012.13.3.945
  21. Töpfer K, Kempe S, Müller N, et al (2011). Tumor evasion from T cell surveillance. J Biomed Biotechnol, 2011, 918471.
  22. Wang W, Zheng Z, Yu W, et al (2012). Polymorphisms of the Fas and FasL genes and risk of breast cancer. Oncol Lett, 3, 625-8.
  23. Weinberg MA, Estefan DJ (2002). Assessing oral malignancies. Am Fam Physician, 65, 1379-84.
  24. Wu W, Wang HD, Guo W, et al (2010). Up-regulation of Fas reverses cisplatin resistance of human small cell lung cancer cells. J Exp Clin Cancer Res, 29, 49-56. https://doi.org/10.1186/1756-9966-29-49
  25. Younes M, Schwartz MR, Ertan A, et al (2000). Fas ligand expression in esophageal carcinomas and their lymph node metastases. Cancer, 88, 524-8. https://doi.org/10.1002/(SICI)1097-0142(20000201)88:3<524::AID-CNCR5>3.0.CO;2-U
  26. Zeytun A, Hassuneh M, Nagarkatti M, et al (1997). Fas-Fas ligand-based interactions between tumor cells and tumorspecific cytotoxic T lymphocytes: a lethal two-way street. Blood, 90, 1952-9.
  27. Zhou JH, Chen HZ, Ye F, et al (2006). Fas-mediated pathway and apoptosis in normal cervix, cervical intraepithelial neoplasia and cervical squamous cancer. Oncol Rep, 16, 307-11.
  28. Zielińska K, Kozlowska K, Cichorek M, et al (2008). Fas and FasL expression on cells of two transplantable melanoma lines according to their different biological properties. Folia Histochem Cytobiol, 46, 337-43.

Cited by

  1. Association of Serum and Salivary Tumor Necrosis Factor-α with Histological Grading in Oral Cancer and its Role in Differentiating Premalignant and Malignant Oral Disease vol.15, pp.17, 2014, https://doi.org/10.7314/APJCP.2014.15.17.7141
  2. β-elemene Induces Caspase-dependent Apoptosis in Human Glioma Cells in vitro through the Upregulation of Bax and Fas/FasL and Downregulation of Bcl-2 vol.15, pp.23, 2015, https://doi.org/10.7314/APJCP.2014.15.23.10407
  3. The role of CD95 and CD95 ligand in cancer vol.22, pp.4, 2015, https://doi.org/10.1038/cdd.2015.3
  4. Expression of ADAM10, Fas, FasL and Soluble FasL in Patients with Oral Squamous Cell Carcinoma (OSCC) and their Association with Clinical-Pathological Parameters vol.23, pp.2, 2017, https://doi.org/10.1007/s12253-016-0102-5
  5. A novel mechanism of rs763110 polymorphism contributing to cervical cancer risk by affecting the binding affinity of C/EBPβ and OCT1 complex to chromatin vol.140, pp.4, 2016, https://doi.org/10.1002/ijc.30490
  6. Molecular Markers of Anticancer Drug Resistance in Head and Neck Squamous Cell Carcinoma: A Literature Review vol.10, pp.10, 2018, https://doi.org/10.3390/cancers10100376