title: Downregulation of thrombospondin-1 by DNA hypermethylation is associated with tumor progression in laryngeal squamous cell carcinoma.
abstract: Thrombospondin‑1 (THBS‑1) has been demonstrated to have a complicated role in human cancer and to exert stimulatory and inhibitory effects in different types of tumors. DNA methylation, as the most frequent mechanism for gene silencing, has been widely investigated in regards to the development of tumors. However, the expression levels and methylation status of THBS‑1, and their roles in laryngeal squamous cell carcinoma (LSCC) remain to be elucidated. The present study detected downregulated THBS‑1 mRNA and protein expression levels in LSCC by using reverse transcription-quantitative polymerase chain reaction (PCR) and western blotting, while decreased expression levels of THBS‑1 mRNA and protein were significantly associated with lymph node metastasis and tumor‑node‑metastasis (TNM) stage. Furthermore, aberrant methylation of THBS‑1 was frequently observed in LSCC by methylation‑specific PCR, particularly in tumor tissues from lymph node metastasis or samples from cancer with advanced TNM stage. Furthermore, the current study demonstrated that downregulated expression of THBS‑1 in LSCC was consistent with aberrant methylation of this gene. Treatment with the DNA methyltransferase inhibitor 5-aza-2'-deoxy-cytidine in Hep‑2 cells induced demethylation of THBS-1, enhanced THBS‑1 expression, and inhibited the proliferative and invasive ability of Hep‑2 cells. Collectively, the results of the present study suggest that THBS‑1 may exert an inhibitory effect in the development of LSCC. Aberrant methylation was an important reason for the downregulation of THBS‑1 and was involved in the invasion and metastasis of LSCC. Demethylating agents may be effective candidates for the treatment of LSCC.
authors.affiliation: Department of Head and Neck Surgery, Chongqing Cancer Institute, Chongqing 400030, P.R. China.
authors.forename: Chuang
authors.initials: C
authors.lastname: Huang
authors.affiliation: Department of Head and Neck Surgery, Chongqing Cancer Institute, Chongqing 400030, P.R. China.
authors.forename: Xiaohong
authors.initials: X
authors.lastname: Zhou
authors.affiliation: Department of Head and Neck Surgery, Chongqing Cancer Institute, Chongqing 400030, P.R. China.
authors.forename: Zhenhua
authors.initials: Z
authors.lastname: Li
authors.affiliation: Department of Head and Neck Surgery, Chongqing Cancer Institute, Chongqing 400030, P.R. China.
authors.forename: Hong
authors.initials: H
authors.lastname: Liu
authors.affiliation: Department of Head and Neck Surgery, Chongqing Cancer Institute, Chongqing 400030, P.R. China.
authors.forename: Yun
authors.initials: Y
authors.lastname: He
authors.affiliation: Department of Head and Neck Surgery, Chongqing Cancer Institute, Chongqing 400030, P.R. China.
authors.forename: Guo
authors.initials: G
authors.lastname: Ye
authors.affiliation: Department of Dermatology, The First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, P.R. China.
authors.forename: Kun
authors.initials: K
authors.lastname: Huang
mesh_terms: D000328:Adult; D000368:Aged; D000964:Antimetabolites, Antineoplastic / Q000494:pharmacology; D001374:Azacitidine / Q000031:analogs & derivatives / Q000494:pharmacology; D002294:Carcinoma, Squamous Cell / Q000235:genetics* / Q000473:pathology*; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D019175:DNA Methylation / Q000187:drug effects; D000077209:Decitabine; D018450:Disease Progression; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D007822:Laryngeal Neoplasms / Q000235:genetics* / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D060787:Neoplasm Grading; D009362:Neoplasm Metastasis; D009367:Neoplasm Staging; D019700:Thrombospondin 1 / Q000235:genetics*; D015533:Transcriptional Activation / Q000187:drug effects
chemical_list: D000964:Antimetabolites, Antineoplastic; D019700:Thrombospondin 1; D000077209:Decitabine; D001374:Azacitidine