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

Abdelbaset-Ismail A, Pedziwiatr D, Suszyńska E, Sluczanowska-Glabowska S, Schneider G, Kakar SS, Ratajczak MZ - J Ovarian Res (2016)

Bottom Line: We evaluated expression of Vitamin D3 receptor (VDR) in these cells as well as effect of vitamin D3 exposure on cell proliferation and migration.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.We found that however all normal and malignant germ-line derived cells express functional VDR, Vitamin D3 differently affects their proliferation and migration.

View Article: PubMed Central - PubMed

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

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.

No MeSH data available.


Related in: MedlinePlus

Human and murine germline-derived immortalized cell lines and FACS-sorted very small embryonic-like stem cells (VSELs) and hematopoietic stem cells (HSCs) express functional vitamin D receptors (VDRs). Expression of VDRs was detected in purified mRNA samples from human teratocarcinoma (hNTERA2) and ovarian cancer (hA2780) cell lines (Panel a, left) as well as from the murine embryonal teratocarcinoma (mP19) cell line (Panel b, left) by both real-time and conventional reverse transcription polymerase chain reaction (RT-PCR). The effect of 1,25-dihydroxyvitamin D3 on phosphorylation of p42/44 MAPK and AKTser473 intracellular pathway proteins in hNTERA2 and hA2780 cell lines (Panel a, right) and the mP19 cell line (Panel b, right) was investigated. Cells (2 × 106 cells/mL) were starved for 12 h in their respective basic culture media containing 0.5 % BSA and stimulated afterwards for 5 min with 1,25-dihydroxyvitamin D3 at various concentrations (10−10–10−8 M) or with vehicle (DMSO) only. The experiment was carried out twice with similar results, and representative blots are shown. Panel c The VDR is expressed by sorted VSELs and HSCs. RT-PCR showed expression of the VDR by both murine BM-derived (left panel) and human UCB-derived (right panel) VSELs, HSCs, and MNCs. In all experiments, samples with water only instead of cDNA (−cDNA) and without reverse transcriptase (−RT) were used as negative controls. Representative agarose gels of the RT-PCR amplicons obtained are shown. Each experiment was carried out twice with similar results, and representative blots are shown
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Fig1: Human and murine germline-derived immortalized cell lines and FACS-sorted very small embryonic-like stem cells (VSELs) and hematopoietic stem cells (HSCs) express functional vitamin D receptors (VDRs). Expression of VDRs was detected in purified mRNA samples from human teratocarcinoma (hNTERA2) and ovarian cancer (hA2780) cell lines (Panel a, left) as well as from the murine embryonal teratocarcinoma (mP19) cell line (Panel b, left) by both real-time and conventional reverse transcription polymerase chain reaction (RT-PCR). The effect of 1,25-dihydroxyvitamin D3 on phosphorylation of p42/44 MAPK and AKTser473 intracellular pathway proteins in hNTERA2 and hA2780 cell lines (Panel a, right) and the mP19 cell line (Panel b, right) was investigated. Cells (2 × 106 cells/mL) were starved for 12 h in their respective basic culture media containing 0.5 % BSA and stimulated afterwards for 5 min with 1,25-dihydroxyvitamin D3 at various concentrations (10−10–10−8 M) or with vehicle (DMSO) only. The experiment was carried out twice with similar results, and representative blots are shown. Panel c The VDR is expressed by sorted VSELs and HSCs. RT-PCR showed expression of the VDR by both murine BM-derived (left panel) and human UCB-derived (right panel) VSELs, HSCs, and MNCs. In all experiments, samples with water only instead of cDNA (−cDNA) and without reverse transcriptase (−RT) were used as negative controls. Representative agarose gels of the RT-PCR amplicons obtained are shown. Each experiment was carried out twice with similar results, and representative blots are shown

Mentions: Figure 1a, b, left panels show that the human ovarian cancer cell line (A2780) as well as the human (NTERA2) and murine (P190) teratocarcinoma cell lines express mRNA for the VDR. Importantly, we provide evidence that stimulation by vitamin D3 induces phosphorylation of MAPKp42/44 and AKTser473 in these cells (Fig. 1a, b, right panels). Next, we isolated mRNA from human and murine VSELs and the corresponding hematopoietic stem cells (HSCs) and detected expression of VDR mRNA in all these cells. As expected, the VDR was also expressed in peripheral blood mononuclear cells (MNCs, Fig. 1c, left and right panels).Fig. 1


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

Abdelbaset-Ismail A, Pedziwiatr D, Suszyńska E, Sluczanowska-Glabowska S, Schneider G, Kakar SS, Ratajczak MZ - J Ovarian Res (2016)

Human and murine germline-derived immortalized cell lines and FACS-sorted very small embryonic-like stem cells (VSELs) and hematopoietic stem cells (HSCs) express functional vitamin D receptors (VDRs). Expression of VDRs was detected in purified mRNA samples from human teratocarcinoma (hNTERA2) and ovarian cancer (hA2780) cell lines (Panel a, left) as well as from the murine embryonal teratocarcinoma (mP19) cell line (Panel b, left) by both real-time and conventional reverse transcription polymerase chain reaction (RT-PCR). The effect of 1,25-dihydroxyvitamin D3 on phosphorylation of p42/44 MAPK and AKTser473 intracellular pathway proteins in hNTERA2 and hA2780 cell lines (Panel a, right) and the mP19 cell line (Panel b, right) was investigated. Cells (2 × 106 cells/mL) were starved for 12 h in their respective basic culture media containing 0.5 % BSA and stimulated afterwards for 5 min with 1,25-dihydroxyvitamin D3 at various concentrations (10−10–10−8 M) or with vehicle (DMSO) only. The experiment was carried out twice with similar results, and representative blots are shown. Panel c The VDR is expressed by sorted VSELs and HSCs. RT-PCR showed expression of the VDR by both murine BM-derived (left panel) and human UCB-derived (right panel) VSELs, HSCs, and MNCs. In all experiments, samples with water only instead of cDNA (−cDNA) and without reverse transcriptase (−RT) were used as negative controls. Representative agarose gels of the RT-PCR amplicons obtained are shown. Each experiment was carried out twice with similar results, and representative blots are shown
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Fig1: Human and murine germline-derived immortalized cell lines and FACS-sorted very small embryonic-like stem cells (VSELs) and hematopoietic stem cells (HSCs) express functional vitamin D receptors (VDRs). Expression of VDRs was detected in purified mRNA samples from human teratocarcinoma (hNTERA2) and ovarian cancer (hA2780) cell lines (Panel a, left) as well as from the murine embryonal teratocarcinoma (mP19) cell line (Panel b, left) by both real-time and conventional reverse transcription polymerase chain reaction (RT-PCR). The effect of 1,25-dihydroxyvitamin D3 on phosphorylation of p42/44 MAPK and AKTser473 intracellular pathway proteins in hNTERA2 and hA2780 cell lines (Panel a, right) and the mP19 cell line (Panel b, right) was investigated. Cells (2 × 106 cells/mL) were starved for 12 h in their respective basic culture media containing 0.5 % BSA and stimulated afterwards for 5 min with 1,25-dihydroxyvitamin D3 at various concentrations (10−10–10−8 M) or with vehicle (DMSO) only. The experiment was carried out twice with similar results, and representative blots are shown. Panel c The VDR is expressed by sorted VSELs and HSCs. RT-PCR showed expression of the VDR by both murine BM-derived (left panel) and human UCB-derived (right panel) VSELs, HSCs, and MNCs. In all experiments, samples with water only instead of cDNA (−cDNA) and without reverse transcriptase (−RT) were used as negative controls. Representative agarose gels of the RT-PCR amplicons obtained are shown. Each experiment was carried out twice with similar results, and representative blots are shown
Mentions: Figure 1a, b, left panels show that the human ovarian cancer cell line (A2780) as well as the human (NTERA2) and murine (P190) teratocarcinoma cell lines express mRNA for the VDR. Importantly, we provide evidence that stimulation by vitamin D3 induces phosphorylation of MAPKp42/44 and AKTser473 in these cells (Fig. 1a, b, right panels). Next, we isolated mRNA from human and murine VSELs and the corresponding hematopoietic stem cells (HSCs) and detected expression of VDR mRNA in all these cells. As expected, the VDR was also expressed in peripheral blood mononuclear cells (MNCs, Fig. 1c, left and right panels).Fig. 1

Bottom Line: We evaluated expression of Vitamin D3 receptor (VDR) in these cells as well as effect of vitamin D3 exposure on cell proliferation and migration.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.We found that however all normal and malignant germ-line derived cells express functional VDR, Vitamin D3 differently affects their proliferation and migration.

View Article: PubMed Central - PubMed

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

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.

No MeSH data available.


Related in: MedlinePlus