Tags

Type your tag names separated by a space and hit enter

Expression of TNF-related apoptosis-inducing ligand in human hepatocellular carcinoma.
Int J Oncol. 2005 May; 26(5):1273-81.IJ

Abstract

TNF-related apoptosis-inducing ligand (TRAIL), as well as Fas ligand, plays a pivotal role in lymphocyte cytotoxicity and the maintenance of immunological homeostasis in various tissues, but its physiological role in immune evasion of cancer cells remains unknown. We have previously shown strong resistance to TRAIL-induced cytotoxicity in human hepatocellular carcinomas (HCCs). The current study investigates the expression of TRAIL in HCCs. We found that three HCC cells, HepG2, Hep3B and Huh7 cells, constitutively express TRAIL mRNA and protein, as detected by reverse transcriptase PCR and Western blotting. Four of 10 human HCC tissues demonstrated positive staining for TRAIL, whereas non-tumor tissues showed little detectable staining. TRAIL expression on tumor cells was detected by flow cytometry and was dramatically induced after the addition of doxorubicin, a chemotherapeutic agent, or cytokine stimulation with TNF-alpha, IL-1beta or IL-18. This expression was induced principally via the NF-kappaB activation pathway, since IkappaB transfection significantly reduced TRAIL expression. In addition, the expressed TRAIL was functional. The TRAIL on HCC cells induced apoptosis in Jurkat cells that are sensitive to TRAIL-mediated apoptosis, and this process was specifically inhibited by recombinant TRAIL-receptors:Fc which binds to TRAIL. In conclusion, TRAIL expressed on the surface of HCC cells by cytokines or cytostatic drugs might contribute to an alternative mechanism that enables tumors to evade immune surveillance by inducing apoptosis of activated human lymphocytes.

Authors+Show Affiliations

First Department of Internal Medicine, Mie University School of Medicine, Tsu, Mie 514-8507, Japan. katsuyas@clin.medic.mie-u.ac.jpNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

15809718

Citation

Shiraki, Katsuya, et al. "Expression of TNF-related Apoptosis-inducing Ligand in Human Hepatocellular Carcinoma." International Journal of Oncology, vol. 26, no. 5, 2005, pp. 1273-81.
Shiraki K, Yamanaka T, Inoue H, et al. Expression of TNF-related apoptosis-inducing ligand in human hepatocellular carcinoma. Int J Oncol. 2005;26(5):1273-81.
Shiraki, K., Yamanaka, T., Inoue, H., Kawakita, T., Enokimura, N., Okano, H., Sugimoto, K., Murata, K., & Nakano, T. (2005). Expression of TNF-related apoptosis-inducing ligand in human hepatocellular carcinoma. International Journal of Oncology, 26(5), 1273-81.
Shiraki K, et al. Expression of TNF-related Apoptosis-inducing Ligand in Human Hepatocellular Carcinoma. Int J Oncol. 2005;26(5):1273-81. PubMed PMID: 15809718.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Expression of TNF-related apoptosis-inducing ligand in human hepatocellular carcinoma. AU - Shiraki,Katsuya, AU - Yamanaka,Takenari, AU - Inoue,Hidekazu, AU - Kawakita,Tomoyuki, AU - Enokimura,Naoyuki, AU - Okano,Hiroshi, AU - Sugimoto,Kazushi, AU - Murata,Kazumoto, AU - Nakano,Takeshi, PY - 2005/4/6/pubmed PY - 2005/7/13/medline PY - 2005/4/6/entrez SP - 1273 EP - 81 JF - International journal of oncology JO - Int J Oncol VL - 26 IS - 5 N2 - TNF-related apoptosis-inducing ligand (TRAIL), as well as Fas ligand, plays a pivotal role in lymphocyte cytotoxicity and the maintenance of immunological homeostasis in various tissues, but its physiological role in immune evasion of cancer cells remains unknown. We have previously shown strong resistance to TRAIL-induced cytotoxicity in human hepatocellular carcinomas (HCCs). The current study investigates the expression of TRAIL in HCCs. We found that three HCC cells, HepG2, Hep3B and Huh7 cells, constitutively express TRAIL mRNA and protein, as detected by reverse transcriptase PCR and Western blotting. Four of 10 human HCC tissues demonstrated positive staining for TRAIL, whereas non-tumor tissues showed little detectable staining. TRAIL expression on tumor cells was detected by flow cytometry and was dramatically induced after the addition of doxorubicin, a chemotherapeutic agent, or cytokine stimulation with TNF-alpha, IL-1beta or IL-18. This expression was induced principally via the NF-kappaB activation pathway, since IkappaB transfection significantly reduced TRAIL expression. In addition, the expressed TRAIL was functional. The TRAIL on HCC cells induced apoptosis in Jurkat cells that are sensitive to TRAIL-mediated apoptosis, and this process was specifically inhibited by recombinant TRAIL-receptors:Fc which binds to TRAIL. In conclusion, TRAIL expressed on the surface of HCC cells by cytokines or cytostatic drugs might contribute to an alternative mechanism that enables tumors to evade immune surveillance by inducing apoptosis of activated human lymphocytes. SN - 1019-6439 UR - https://www.unboundmedicine.com/medline/citation/15809718/Expression_of_TNF_related_apoptosis_inducing_ligand_in_human_hepatocellular_carcinoma_ L2 - https://www.spandidos-publications.com/ijo/26/5/1273 DB - PRIME DP - Unbound Medicine ER -