1,25-Dihydroxyvitamin D3 and a superagonistic analog in combination with paclitaxel or suberoylanilide hydroxamic acid have potent antiproliferative effects on anaplastic thyroid cancer

Clinckspoor, Isabelle; Verlinden, Lieve; Overbergh, Lutgart; Korch, Christopher; Bouillon, Roger; Mathieu, Chantal; Verstuyf, Annemieke; Decallonne, Brigitte

doi:10.1016/j.jsbmb.2010.12.008

Cited by 33 publications

(34 citation statements)

References 38 publications

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“…These molecules are also well known to be targeted by 1,25(OH) (Liu et al 2002;Dackiw et al 2004;Liu et al 2005;Clinckspoor et al 2011). Similarly, in the present study, the decreased VDR and CYP24A1 mRNA expression in PTC N 1 was accompanied by a decreased p21 expression, and we observed a significant positive correlation between VDR and CYP24A1 with p21, a cyclin-dependent kinase inhibitor.…”

supporting

confidence: 87%

“…Increased vitamin D metabolism has also been described in several other benign and malignant tumors (ovarium, endometrium, colon, breast) (Segersten et al 2005;Agic et al 2007;McCarthy et al 2009;Horvath et al 2010;Silvagno et al 2010), and 1,25(OH) 2 D 3 is known to exert antiproliferative effects on several cancer types (Dackiw et al 2004;Bouillon et al 2006;Clinckspoor et al 2011). However, other groups reported decreased VDR, CYP24A1, or CYP27B1 expression in cancerous tissue (benign/malignant) compared with normal tissue, such as for breast, colon, and kidney cancer (Lurie et al 2007;Wada et al 2009;Blomberg et al 2010).…”

Section: Discussionmentioning

confidence: 99%

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Altered Expression of Key Players in Vitamin D Metabolism and Signaling in Malignant and Benign Thyroid Tumors

Clinckspoor

Hauben

Verlinden

et al. 2012

J Histochem Cytochem.

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1,25-DihydroxyvitaminD3 (1,25(OH)2D3), the active form of vitamin D, mediates antitumor effects in various cancers. The expression of key players in vitamin D signaling in thyroid tumors was investigated. Vitamin D receptor (VDR) and CYP27B1 and CYP24A1 (respectively activating and catabolizing vitamin D) expression was studied (RT-PCR, immunohistochemistry) in normal thyroid, follicular adenoma (FA), differentiated thyroid cancer (DTC) consisting of the papillary (PTC) and follicular (FTC) subtype, and anaplastic thyroid cancer (ATC). VDR, CYP27B1, and CYP24A1 expression was increased in FA and DTC compared with normal thyroid. However, in PTC with lymph node metastasis, VDR and CYP24A1 were decreased compared with non-metastasized PTC. In ATC, VDR expression was often lost, whereas CYP27B1/CYP24A1 expression was comparable to DTC. Moreover, ATC with high Ki67 expression (>30%) or distant metastases at diagnosis was characterized by more negative VDR/CYP24A1/CYP27B1 staining. In conclusion, increased expression of key players involved in local 1,25(OH)2D3 signaling was demonstrated in benign and differentiated malignant thyroid tumors, but a decrease was observed for local nodal and especially distant metastasis, suggesting a local antitumor response of 1,25(OH)2D3 in early cancer stages. These findings advocate further studies with 1,25(OH)2D3 and analogs in persistent and recurrent iodine-refractory DTC.

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supporting

confidence: 87%

Section: Discussionmentioning

confidence: 99%

Altered Expression of Key Players in Vitamin D Metabolism and Signaling in Malignant and Benign Thyroid Tumors

Clinckspoor

Hauben

Verlinden

et al. 2012

J Histochem Cytochem.

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“…Supraphysiological doses of active vitamin D have been described to inhibit proliferation and reduce the severity of autoimmunity in case of underlying malignant or autoimmune thyroid disease, respectively [5,6,11]. In the present study, global thyroid morphology was unchanged in VDR-KO mice, also after correction of the hypocalcemic state, and no signs of autoimmune thyroiditis or thyroid neoplasia were present.…”

Section: Discussionsupporting

confidence: 49%

“…We and others have shown that high doses of 1,25(OH) 2 D 3 or structural analogues have antiproliferative effects in human thyroid cancer cell lines [5,6,7]. On the other hand, data on a possible association between vitamin D deficiency and increased risk for thyroid cancer are scarce and debated [8,9,10].…”

Section: Introductionmentioning

confidence: 99%

The Vitamin D Receptor in Thyroid Development and Function

et al. 2012

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Background and Objective: Vitamin D is known to modulate thyroid neoplastic and autoimmune disease. We investigated the role of the vitamin D receptor (VDR) in normal thyroid development and function (thyrocytes and C cells). Methods: The thyroid phenotype of VDR knockout mice was studied in comparison to wild-type controls. The mice were fed a normal diet or a calcium-rich diet to circumvent effects induced by hypocalcemia. Results: Thyroid morphology was unaltered in VDR knockout mice. Also, expression of different parameters of thyrocyte function was comparable (immunohistochemistry). C cell physiology was, however, affected in the absence of the VDR, resulting in increased thyroidal calcitonin expression (immunohistochemistry), paralleled by increased serum calcitonin levels, but only in normocalcemic mice. To study a possible effect of vitamin D status on basal calcitonin levels in humans, serum calcitonin concentrations were compared between vitamin D-deficient and -sufficient patients (serum 25-OH vitamin D₃ ≤10 and ≥40 ng/ml, respectively), but no difference was observed. Conclusions: In mice, the VDR is redundant for normal thyrocyte function, but not for C cell function, where it mediates the negative control of calcitonin by 1,25-dihydroxyvitamin D₃. In patients, vitamin D status does not affect basal serum calcitonin levels. A study in healthy individuals is needed to confirm these findings.

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“…Furthermore, VDR polymorphisms have been associated with differentiated thyroid cancer [31,32]. As for ATC, 1α,25(OH)2D3 and a superagonistic analog (CD578) in combination with paclitaxel or suberoylanilide hydroxamic acid have been shown to have potent antiproliferative effects on ATC [33]. In the present study, we aimed to investigate the effects of 1α,25(OH)2D3 and the newly synthesized analog, MART-10, on the metastatic ability of undifferentiated thyroid cancer cells.…”

Section: Discussionmentioning

confidence: 99%

MART-10, the vitamin D analog, is a potent drug to inhibit anaplastic thyroid cancer cell metastatic potential

et al. 2015

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1,25-Dihydroxyvitamin D3 and a superagonistic analog in combination with paclitaxel or suberoylanilide hydroxamic acid have potent antiproliferative effects on anaplastic thyroid cancer

Cited by 33 publications

References 38 publications

Altered Expression of Key Players in Vitamin D Metabolism and Signaling in Malignant and Benign Thyroid Tumors

Altered Expression of Key Players in Vitamin D Metabolism and Signaling in Malignant and Benign Thyroid Tumors

The Vitamin D Receptor in Thyroid Development and Function

MART-10, the vitamin D analog, is a potent drug to inhibit anaplastic thyroid cancer cell metastatic potential

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