Aberrant L1 cell adhesion molecule affects tumor behavior and chemosensitivity in anaplastic thyroid carcinoma

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Title
Aberrant L1 cell adhesion molecule affects tumor behavior and chemosensitivity in anaplastic thyroid carcinoma
Author(s)
K S Kim; Jeong Ki Min; Z L Liang; Gyungmin Lee; J U Lee; Kwang-Hee Bae; M H Lee; S E Lee; M J Ryu; S J Kim; Y K Kim; M J Choi; Y S Jo; J M Kim; M Shong
Bibliographic Citation
Clinical Cancer Research, vol. 18, no. 11, pp. 3071-3078
Publication Year
2012
Abstract
Purpose: 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. Experimental Design: 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 chemosensitivityto 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.
ISSN
1078-0432
Publisher
Amer Assoc Cancer Research
DOI
http://dx.doi.org/10.1158/1078-0432.CCR-11-2757
Type
Article
Appears in Collections:
Division of Biomedical Research > Biotherapeutics Translational Research Center > 1. Journal Articles
Division of Biomedical Research > Metabolic Regulation Research Center > 1. Journal Articles
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