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维生素D3刺激胚胎干细胞,但抑制卵巢癌和畸胎癌细胞系的迁移和生长。

Vitamin D3 stimulates embryonic stem cells but inhibits migration and growth of ovarian cancer and teratocarcinoma cell lines.

作者信息

Abdelbaset-Ismail Ahmed, Pedziwiatr Daniel, Suszyńska Ewa, Sluczanowska-Glabowska Sylwia, Schneider Gabriela, Kakar Sham S, Ratajczak Mariusz Z

机构信息

Stem Cell Institute at James Graham Brown Cancer Center, University of Louisville, 500 S. Floyd Street, Rm. 107, Louisville, KY, 40202, USA.

Department of Physiology Pomeranian Medical University, Szczecin, Poland.

出版信息

J Ovarian Res. 2016 Apr 18;9:26. doi: 10.1186/s13048-016-0235-x.

Abstract

BACKGROUND

Deficiency in Vitamin D3 (cholecalciferol) may predispose to some malignancies, including gonadal tumors and in experimental models vitamin D3 has been proven to inhibit the growth of cancer cells. To learn more about the potential role of vitamin D3 in cancerogenesis, we evaluated the expression and functionality of the vitamin D receptor (VDR) and its role in metastasis of ovarian cancer cells and of murine and human teratocarcinoma cell lines.

METHODS

In our studies we employed murine embrynic stem cells (ESD3), murine (P19) and human (NTERA-2) teratocarcimona cells lines, human ovarian cancer cells (A2780) as well as purified murine and human purified very small embryonic like stem cells (VSELs). We evaluated expression of Vitamin D3 receptor (VDR) in these cells as well as effect of vitamin D3 exposure on cell proliferation and migration.

RESULTS

We here provide also more evidence for the role of vitamin D3 in germline-derived malignancies, and this evidence supports the proposal that vitamin D3 treatment inhibits growth and metastatic potential of several germline-derived malignancies. We also found that the ESD3 murine immortalized embryonic stem cell line and normal, pluripotent, germline-marker-positive very small embryonic-like stem cells (VSELs) isolated from adult tissues are stimulated by vitamin D3, which suggests that vitamin D3 affects the earliest stages of embryogenesis.

CONCLUSIONS

We found that however all normal and malignant germ-line derived cells express functional VDR, Vitamin D3 differently affects their proliferation and migration. We postulate that while Vitamin D3 as anticancer drug inhibits proliferation of malignant cells, it may protect normal stem cells that play an important role in development and tissue/organ regeneration.

摘要

背景

维生素D3(胆钙化醇)缺乏可能易患某些恶性肿瘤,包括性腺肿瘤,并且在实验模型中已证明维生素D3可抑制癌细胞生长。为了更多地了解维生素D3在癌症发生中的潜在作用,我们评估了维生素D受体(VDR)的表达和功能及其在卵巢癌细胞以及小鼠和人畸胎瘤细胞系转移中的作用。

方法

在我们的研究中,我们使用了小鼠胚胎干细胞(ESD3)、小鼠(P19)和人(NTERA-2)畸胎瘤细胞系、人卵巢癌细胞(A2780)以及纯化的小鼠和人纯化的非常小的胚胎样干细胞(VSELs)。我们评估了这些细胞中维生素D3受体(VDR)的表达以及维生素D3暴露对细胞增殖和迁移的影响。

结果

我们在此还提供了更多证据证明维生素D3在生殖系来源的恶性肿瘤中的作用,并且该证据支持维生素D3治疗可抑制几种生殖系来源的恶性肿瘤的生长和转移潜能这一观点。我们还发现,ESD3小鼠永生化胚胎干细胞系以及从成年组织中分离出的正常、多能、生殖系标记阳性的非常小的胚胎样干细胞(VSELs)受到维生素D3的刺激,这表明维生素D3影响胚胎发育的最早阶段。

结论

我们发现,尽管所有正常和恶性生殖系来源的细胞都表达功能性VDR,但维生素D3对它们的增殖和迁移有不同影响。我们推测,虽然维生素D3作为抗癌药物可抑制恶性细胞的增殖,但它可能保护在发育和组织/器官再生中起重要作用的正常干细胞。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/af30/4835879/c9cb807d5311/13048_2016_235_Fig1_HTML.jpg

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