MART-10, the vitamin D analog, is a potent drug to inhibit anaplastic thyroid cancer cell metastatic potential.
The survival rate of anaplastic thyroid cancer (ATC) is still very poor due to its fast growth and high metastatic potential. Currently, no effective treatment is available. The active form of vitamin D3, 1α,25(OH)2D3, has been shown to have a anti-metastatic effect in pre-clinical studies, however induction of hypercalcemia hampered its clinical application. The new class of less-calcemic vitamin D analog, 19-nor-2α-(3-hydroxypropyl)-1α,25-dihydroxyvitamin D3 (MART-10), is much more potent than 1α,25(OH)2D3 to repress cancer growth and metastasis in a variety of cancers. In this study, we demonstrated that both 1α,25(OH)2D3 and MART-10 could effectively inhibit the migration and invasion of ATC cells, 8305C and 8505C, with MART-10 much more potent than 1α,25(OH)2D3. The anti-metastatic effect of 1α,25(OH)2D3 and MART-10 on ATC cells is mediated by reversal of cadherin switch (upregulation of E-cadherin and downregulation of N-cadherin), which led to the attenuation of EMT process, and decrease of F-actin formation. We further showed that the expressions of Slug, the EMT-related transcriptional factor, and MMP-9 were inhibited by 1α,25(OH)2D3 and MART-10 in 8505C cells, but not in 8303C cells. Since metastasis is the important cause of ATC-related death, our results strongly encourage the further in vivo study of MART-10 application against ATC.
General Surgery Department, Chang Gung Memorial Hospital, Chung Gung University, Kwei-Shan, Taoyuan, Taiwan; Thyroid Cancer Team, Keelung Chang Gung Cancer Center, Keelung, Taiwan.
Kun-Chun
KC
Chiang
Thyroid Cancer Team, Keelung Chang Gung Cancer Center, Keelung, Taiwan; Department of Endocrinology and Metabolism, Chang Gung Memorial Hospital, Chung Gung University, Keelung, Taiwan.
Sheng-Fong
SF
Kuo
Thyroid Cancer Team, Keelung Chang Gung Cancer Center, Keelung, Taiwan; Department of Endocrinology and Metabolism, Chang Gung Memorial Hospital, Chung Gung University, Keelung, Taiwan.
Chih-Hung
CH
Chen
Thyroid Cancer Team, Keelung Chang Gung Cancer Center, Keelung, Taiwan; Department of Endocrinology and Metabolism, Chang Gung Memorial Hospital, Chung Gung University, Keelung, Taiwan.
Sohching
S
Ng
Department of Endocrinology and Metabolism, Chang Gung Memorial Hospital, Chang Gung University, Kwei-Shan, Taoyuan 333, Taiwan.
Shu-Fu
SF
Lin
General Surgery Department, Chang Gung Memorial Hospital, Chung Gung University, Kwei-Shan, Taoyuan, Taiwan.
Chun-Nan
CN
Yeh
Department of Gastroenterology, Chang Gung Memorial Hospital, Chung Gung University, Keelung, Taiwan.
Li-Wei
LW
Chen
Faculty of Pharmaceutical Sciences, Teikyo University, 2-11-1 Kaga, Itabashi, Tokyo, Japan.
Masashi
M
Takano
Boston University School of Medicine, Boston, MA 02118, USA.
Tai C
TC
Chen
Department of Anatomy, College of Medicine, Chang Gung University, Kwei-Shan, Taoyuan 333, Taiwan.
Horng-Heng
HH
Juang
Faculty of Pharmaceutical Sciences, Teikyo University, 2-11-1 Kaga, Itabashi, Tokyo, Japan. Electronic address: akittaka@pharm.teikyo-u.ac.jp.
Atsushi
A
Kittaka
Department of Endocrinology and Metabolism, Chang Gung Memorial Hospital, Chang Gung University, Kwei-Shan, Taoyuan 333, Taiwan. Electronic address: einjd@adm.cgmh.org.tw.
Jen-Der
JD
Lin
Graduate Institute of Clinical Medical Sciences, College of Medicine, Chang Gung University, Kwei-Shan, Taoyuan, Taiwan. Electronic address: jonghwei@mail.cgu.edu.tw.
Jong-Hwei S
JH
Pang
D000199:Actins; D000970:Antineoplastic Agents / Q000494:pharmacology*; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects*; D002762:Cholecalciferol / Q000031:analogs & derivatives* / Q000494:pharmacology; D004354:Drug Screening Assays, Antitumor; D058750:Epithelial-Mesenchymal Transition; D006801:Humans; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D009362:Neoplasm Metastasis; D013964:Thyroid Neoplasms / Q000188:drug therapy*
C569618:19-nor-2-(3-hydroxypropyl)-1,25-dihydroxyvitamin D3; D000199:Actins; D000970:Antineoplastic Agents; D002762:Cholecalciferol; C522361:MMP2 protein, human; D020778:Matrix Metalloproteinase 2; C579270:MMP9 protein, human; D020780:Matrix Metalloproteinase 9
Anaplastic thyroid cancer; EMT; Invasion; MART-10; Migration; Vitamin D