Inhibitory effects of retinoic acid on invasiveness of human thyroid carcinoma cell lines in vitro.
BACKGROUND
The prognosis of patients with metastasized thyroid carcinoma is not optimistic, necessitating the search for new treatment options.


OBJECTIVE
Beneficial effects of retinoic acid (RA) have been suggested in thyroid cancer differentiation and the present study was performed to investigate the anti-metastatic potential of RA in respect of important determinants of metastatic behavior in thyroid carcinoma, focusing on the role of invasion-associated proteins.


METHODS
Differentiated thyroid carcinoma cell lines FTC- 133 and XTC.UC1, and anaplastic thyroid cancer cell lines C643 and HTH74 were studied. All cell lines were cultured with alltrans- RA (ATRA) or the solvent ethanol. Invasion and adhesion potency in vitro was studied by transwell experiment and short-term adhesion assay. The involvement of invasion-associated proteins, urokinase type plasminogen activator (uPA), uPA receptor (uPAR), matrix metalloproteinase-2 (MMP-2) and E-cadherin, were investigated by semi-quantitative RT-PCR and Western blot.


RESULTS
In vitro invasion assay revealed that ATRA treatment could reduce the invasive potency in all the thyroid cancer cell lines, with the most significant effect in anaplastic cancer cells. Short-term adhesion assay suggested that ATRA increases cancer cell adhesion to extracellular matrix (ECM) in C643, HTH74 and XTC.UC1, probably through a transcriptional and translational regulation of some attachment molecules. RT-PCR andWestern blot both revealed diminished expression of uPAR in all four carcinoma cell lines. In C643 and HTH74 cell lines, the expression of uPA was reduced and the expression of E-cadherin was increased, whereas the MMP-2 expression was not significantly down-regulated in ATRA-treated group. In ATRA-treated FTC-133 and XTC.UC1 cell lines, MMP-2 expression was decreased, but no significant changes in uPA and E-cadherin expression were observed.


CONCLUSIONS
The present study demonstrates the influence of ATRA on both important determinants of metastatic behavior ("de-adhesion" and proteolysis) in thyroid carcinoma cell lines, especially in anaplastic cancer cells. These findings may add to the explanations for beneficial effects of RA in the treatment of metastatic thyroid carcinomas.
Lan
L
L
Department of Endocrinology, Beijing Ji Shui Tan Hospital, the 4th Medical College of Peking University, Xi Chen Qu Xin Jie Kou Dong Jie 31, 100035 Beijing, China. lanjingling0627@hotmail.com
Cui
D
D
Luo
Y
Y
Shi
B Y
BY
Deng
L L
LL
Zhang
G Y
GY
Wang
H
H
D018263:Adenocarcinoma, Follicular / Q000556:secondary; D000328:Adult; D015820:Cadherins / Q000378:metabolism; D002448:Cell Adhesion / Q000187:drug effects; D045744:Cell Line, Tumor; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D008297:Male; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism; D009361:Neoplasm Invasiveness / Q000473:pathology*; D013964:Thyroid Neoplasms / Q000473:pathology* / Q000556:secondary; D014212:Tretinoin / Q000494:pharmacology*; D014568:Urokinase-Type Plasminogen Activator
D015820:Cadherins; D014212:Tretinoin; D014568:Urokinase-Type Plasminogen Activator; D020778:Matrix Metalloproteinase 2