title: The effect of ephrin-A1 on resistance to Photofrin-mediated photodynamic therapy in esophageal squamous cell carcinoma cells.
abstract: Esophageal squamous cell carcinoma (ESCC), the most prevalent cell type of esophageal cancer, remains a dismal disease with poor prognosis. Photodynamic therapy (PDT) is a minimally invasive treatment option for early esophageal cancer. To explore possible factors involved in resistance to PDT in esophageal cancer cells, we selected PDT-resistant subcell lines by repeated treatment of CE48T/VGH (CE48T) ESCC cells with Photofrin-PDT and then analyzed the global gene modulations in the PDT-resistant cells by whole-genome microarray. More than 700 genes reached a fold change greater than 1.5 in each of the PDT-resistant cells compared to parental cells. Among these genes, both tumor necrosis factor (TNF) and EFNA1 genes were significantly upregulated in resistant cell lines. However, they were significantly downregulated in Photofrin-PDT-treated cells compared to untreated cells. The observations made in the microarray analysis were further confirmed by quantitative PCR. We observed that recombinant tumor necrosis factor alpha (TNF-α) activated the gene expression of EFNA1 at both the messenger RNA (mRNA) level and the protein level in CE48T cells. Functional analysis showed that when incubated with oligomeric and monomeric ephrin-A1 simultaneously, ESCC cells became significantly resistant to Photofrin-PDT. Functional analysis further suggested that transmembrane and soluble ephrin-A1 may cooperate to enhance resistance to Photofrin-PDT in ESCC cells.
authors.affiliation: Department of Surgery, National Taiwan University Hospital and National Taiwan University College of Medicine, No. 7, Chung-Shan South Rd., Taipei, Taiwan.
authors.forename: Pei-Wen
authors.initials: PW
authors.lastname: Yang
authors.affiliation: Department of Surgery, National Taiwan University Hospital and National Taiwan University College of Medicine, No. 7, Chung-Shan South Rd., Taipei, Taiwan.
authors.forename: Tzu-Hsuan
authors.initials: TH
authors.lastname: Chiang
authors.affiliation: Department of Surgery, National Taiwan University Hospital and National Taiwan University College of Medicine, No. 7, Chung-Shan South Rd., Taipei, Taiwan.
authors.forename: Ching-Yueh
authors.initials: CY
authors.lastname: Hsieh
authors.affiliation: Department of Surgery, National Taiwan University Hospital and National Taiwan University College of Medicine, No. 7, Chung-Shan South Rd., Taipei, Taiwan.
authors.forename: Ya-Chuan
authors.initials: YC
authors.lastname: Huang
authors.affiliation: Department of Surgery, National Taiwan University Hospital and National Taiwan University College of Medicine, No. 7, Chung-Shan South Rd., Taipei, Taiwan.
authors.forename: Li-Fan
authors.initials: LF
authors.lastname: Wong
authors.affiliation: Department of Molecular and Cellular Oncology, University of Texas M. D. Anderson Cancer Center, Houston, TX, USA.|Center for Molecular Medicine and Graduate Institute of Cancer Biology, China Medical University, Taichung, Taiwan.
authors.forename: Mien-Chie
authors.initials: MC
authors.lastname: Hung
authors.affiliation: Department of Surgery, National Taiwan University Hospital and National Taiwan University College of Medicine, No. 7, Chung-Shan South Rd., Taipei, Taiwan. jctsai@ntu.edu.tw.|Center for Optoelectronic Medicine, National Taiwan University College of Medicine, Taipei, Taiwan. jctsai@ntu.edu.tw.
authors.forename: Jui-Chang
authors.initials: JC
authors.lastname: Tsai
authors.affiliation: Department of Surgery, National Taiwan University Hospital and National Taiwan University College of Medicine, No. 7, Chung-Shan South Rd., Taipei, Taiwan. jmlee@ntu.edu.tw.
authors.forename: Jang-Ming
authors.initials: JM
authors.lastname: Lee
mesh_terms: D002294:Carcinoma, Squamous Cell / Q000188:drug therapy / Q000235:genetics / Q000473:pathology*; D045744:Cell Line, Tumor; D017323:Dihematoporphyrin Ether / Q000494:pharmacology* / Q000627:therapeutic use; D015536:Down-Regulation / Q000187:drug effects / Q000528:radiation effects; D019008:Drug Resistance, Neoplasm / Q000187:drug effects* / Q000528:radiation effects; D036382:Ephrin-A1 / Q000494:pharmacology*; D004938:Esophageal Neoplasms / Q000188:drug therapy / Q000235:genetics / Q000473:pathology*; D000077277:Esophageal Squamous Cell Carcinoma; D006801:Humans; D010778:Photochemotherapy; D017319:Photosensitizing Agents / Q000494:pharmacology* / Q000627:therapeutic use; D015854:Up-Regulation / Q000187:drug effects / Q000528:radiation effects
chemical_list: D036382:Ephrin-A1; D017319:Photosensitizing Agents; D017323:Dihematoporphyrin Ether
keywords: Ephrin-A1 on resistance; Esophageal squamous cell carcinoma cells; Photodynamic therapy