title: Aberrant l1 cell adhesion molecule affects tumor behavior and chemosensitivity in anaplastic thyroid carcinoma.
abstract: OBJECTIVE
  Anaplastic thyroid carcinoma (ATC) is one of the most invasive human cancers and has a poor prognosis. Molecular targets of ATC that determine its highly aggressive nature remain unidentified. This study investigated L1 cell adhesion molecule (L1CAM) expression and its role in tumorigenesis of ATCs.
  
  
  METHODS
  Expression of L1CAM in thyroid cancer was evaluated by immunohistochemical analyses of tumor samples from patients with thyroid cancer. We investigated the role of L1CAM in proliferation, migration, invasion, and chemoresistance using short hairpin RNA (shRNA) knockdown experiments in human ATC cell lines. Finally, we evaluated the role of L1CAM on tumorigenesis with ATC xenograft assay in a nude mouse model.
  
  
  RESULTS
  L1CAM expression was not detectable in normal follicular epithelial cells of the thyroid or in differentiated thyroid carcinoma. In contrast, analysis of ATC samples showed specifically higher expression of L1CAM in the invasive area of the tumor. Specific knockdown of L1CAM in the ATC cell lines, FRO and 8505C, caused a significant decrease in the proliferative, migratory, and invasive capabilities of the cells. Suppression of L1CAM expression in ATC cell lines increased chemosensitivity to gemcitabine or paclitaxel. Finally, in an ATC xenograft model, depletion of L1CAM markedly reduced tumor growth and increased the survival of tumor-bearing mice.
  
  
  CONCLUSIONS
  We report that L1CAM is highly expressed in the samples taken from patients with ATCs. L1CAM plays an important role in determining tumor behavior and chemosensitivity in cell lines derived from ATCs. Therefore, we suggest that L1CAM may be an important therapeutic target in patients with ATCs.
authors.affiliation: Research Center for Endocrinology and Metabolic Diseases, Division of Endocrinology, Department of Internal Medicine, Chungnam National University School of Medicine, Daejeon, South Korea.
authors.forename: Koon Soon
authors.initials: KS
authors.lastname: Kim
authors.forename: Jeong-Ki
authors.initials: JK
authors.lastname: Min
authors.forename: Zhe Long
authors.initials: ZL
authors.lastname: Liang
authors.forename: Kyungmin
authors.initials: K
authors.lastname: Lee
authors.forename: Jung Uee
authors.initials: JU
authors.lastname: Lee
authors.forename: Kwang-Hee
authors.initials: KH
authors.lastname: Bae
authors.forename: Min Hee
authors.initials: MH
authors.lastname: Lee
authors.forename: Seong Eun
authors.initials: SE
authors.lastname: Lee
authors.forename: Min Jeong
authors.initials: MJ
authors.lastname: Ryu
authors.forename: Soung Jung
authors.initials: SJ
authors.lastname: Kim
authors.forename: Yong Kyoung
authors.initials: YK
authors.lastname: Kim
authors.forename: Min Jeong
authors.initials: MJ
authors.lastname: Choi
authors.forename: Young Suk
authors.initials: YS
authors.lastname: Jo
authors.forename: Jin-Man
authors.initials: JM
authors.lastname: Kim
authors.forename: Minho
authors.initials: M
authors.lastname: Shong
mesh_terms: D000818:Animals; D054316:Biomarkers, Pharmacological; D045744:Cell Line, Tumor; D002465:Cell Movement; D049109:Cell Proliferation; D055785:Gene Knockdown Techniques; D006801:Humans; D051379:Mice; D008819:Mice, Nude; D009361:Neoplasm Invasiveness; D009368:Neoplasm Transplantation; D039842:Neural Cell Adhesion Molecule L1 / Q000235:genetics / Q000378:metabolism*; D034741:RNA, Small Interfering; D065646:Thyroid Carcinoma, Anaplastic; D013964:Thyroid Neoplasms / Q000378:metabolism*; D014183:Transplantation, Heterologous
chemical_list: D054316:Biomarkers, Pharmacological; D039842:Neural Cell Adhesion Molecule L1; D034741:RNA, Small Interfering