RRC ID 44748
Author Migita K, Sho M, Shimada K, Yasuda S, Yamato I, Takayama T, Matsumoto S, Wakatsuki K, Hotta K, Tanaka T, Ito M, Konishi N, Nakajima Y.
Title Significant involvement of herpesvirus entry mediator in human esophageal squamous cell carcinoma.
Journal Cancer
Abstract BACKGROUND:Herpesvirus entry mediator (HVEM) is known to regulate immune response and to be expressed in several human malignancies. However, to the authors's knowledge, the precise role of HVEM in human cancer biology remains unknown. The objective of the current study was to clarify the clinical significance of HVEM in human esophageal squamous cell carcinoma as well as its in vivo functions.
METHODS:HVEM expression was evaluated in 103 patients with esophageal squamous cell carcinoma to explore its clinical relevance and prognostic value. The functions of HVEM in tumors were analyzed in vitro and in vivo using the small interfering RNA (siRNA) silencing technique.
RESULTS:HVEM expression was found to be significantly correlated with depth of tumor invasion and lymph node metastasis. Furthermore, it was found to be inversely correlated with tumor-infiltrating CD4(+) , CD8(+) , and CD45RO(+) lymphocytes. It is important to note that HVEM status was identified as an independent prognostic marker. HVEM gene silencing significantly inhibited cancer cell proliferation in vitro and cancer growth in vivo. This antitumor effect was associated with reduced cell proliferation activity. The effect was also correlated with the induction of CD8(+) cells and upregulation of local immune response.
CONCLUSIONS:HVEM plays a critical role in both tumor progression and the evasion of host antitumor immune responses, possibly through direct and indirect mechanisms. Therefore, HVEM may be a promising therapeutic target for human esophageal cancer.
Volume 120(6)
Pages 808-17
Published 2014-3-15
DOI 10.1002/cncr.28491
PMID 24249528
MeSH Aged Animals Biomarkers, Tumor / genetics CD4-Positive T-Lymphocytes / immunology* CD8-Positive T-Lymphocytes / immunology* Carcinoma, Squamous Cell / genetics* Cell Cycle Checkpoints / genetics Cell Line, Tumor Cell Proliferation Cell Survival / genetics Disease Progression Esophageal Neoplasms / genetics* Esophageal Squamous Cell Carcinoma Female Forkhead Transcription Factors / biosynthesis Humans Leukocyte Common Antigens / biosynthesis Lymphatic Metastasis Lymphocyte Activation / genetics Lymphocyte Activation / immunology Male Mice Mice, Inbred BALB C Middle Aged Neoplasm Invasiveness Prognosis RNA Interference RNA, Small Interfering Receptors, Tumor Necrosis Factor, Member 14 / genetics Receptors, Tumor Necrosis Factor, Member 14 / metabolism*
IF 6.537
Times Cited 7
Human and Animal Cells