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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

1,25-dihydroxyvitamin D3 inhibits metastasis of human ovarian cancer and teratocarcinoma cells. Detection of in vivo-transplanted 1,25-dihydroxyvitamin D3-treated A2780 human ovarian cancer cells (a) and hNTERA-2 human teratocarcinoma cells (b) in the organs of irradiated mice post transplantation. As shown, the number of 1,25-dihydroxyvitamin D3-treated cancer cells was significantly lower in isolated organs from mice than in ex vivo-untreated cells (vehicle only). Detection was performed by employing RT-qPCR for the presence of human Alu sequences in purified genomic DNA samples. For statistical comparisons, a one-way analysis of variance and a Tukey’s test for post hoc analysis were carried out, and means ± SD are shown. Significance levels: *p ≤ 0.05, **p ≤ 0.01, ***p ≤ 0.001 versus control (untreated) cells
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Fig5: 1,25-dihydroxyvitamin D3 inhibits metastasis of human ovarian cancer and teratocarcinoma cells. Detection of in vivo-transplanted 1,25-dihydroxyvitamin D3-treated A2780 human ovarian cancer cells (a) and hNTERA-2 human teratocarcinoma cells (b) in the organs of irradiated mice post transplantation. As shown, the number of 1,25-dihydroxyvitamin D3-treated cancer cells was significantly lower in isolated organs from mice than in ex vivo-untreated cells (vehicle only). Detection was performed by employing RT-qPCR for the presence of human Alu sequences in purified genomic DNA samples. For statistical comparisons, a one-way analysis of variance and a Tukey’s test for post hoc analysis were carried out, and means ± SD are shown. Significance levels: *p ≤ 0.05, **p ≤ 0.01, ***p ≤ 0.001 versus control (untreated) cells

Mentions: Next, to assess the effect of vitamin D3 on the metastatic potential of germ line-derived tumor cells in vivo, we exposed A2780 human ovarian cancer (Fig. 5, panel a) and NTERA2 human teratocarcinoma cells (Fig. 5, panel b) to vitamin D3 before i.v. injection into immunodeficient mice. Incubation of tumor cells before injection with vitamin D3 decreased seeding efficiency of these cells into bone marrow, liver, and lung. This decrease in seeding efficiency can again be explained by the combined pro-apoptotic (Fig. 3), anti-proliferative (Fig. 4), anti-migratory (Fig. 2, panel a), and anti-adhesive (Fig. 2, panel b) effects of vitamin D3.Fig. 5


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)

1,25-dihydroxyvitamin D3 inhibits metastasis of human ovarian cancer and teratocarcinoma cells. Detection of in vivo-transplanted 1,25-dihydroxyvitamin D3-treated A2780 human ovarian cancer cells (a) and hNTERA-2 human teratocarcinoma cells (b) in the organs of irradiated mice post transplantation. As shown, the number of 1,25-dihydroxyvitamin D3-treated cancer cells was significantly lower in isolated organs from mice than in ex vivo-untreated cells (vehicle only). Detection was performed by employing RT-qPCR for the presence of human Alu sequences in purified genomic DNA samples. For statistical comparisons, a one-way analysis of variance and a Tukey’s test for post hoc analysis were carried out, and means ± SD are shown. Significance levels: *p ≤ 0.05, **p ≤ 0.01, ***p ≤ 0.001 versus control (untreated) cells
© Copyright Policy - OpenAccess
Related In: Results  -  Collection

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getmorefigures.php?uid=PMC4835879&req=5

Fig5: 1,25-dihydroxyvitamin D3 inhibits metastasis of human ovarian cancer and teratocarcinoma cells. Detection of in vivo-transplanted 1,25-dihydroxyvitamin D3-treated A2780 human ovarian cancer cells (a) and hNTERA-2 human teratocarcinoma cells (b) in the organs of irradiated mice post transplantation. As shown, the number of 1,25-dihydroxyvitamin D3-treated cancer cells was significantly lower in isolated organs from mice than in ex vivo-untreated cells (vehicle only). Detection was performed by employing RT-qPCR for the presence of human Alu sequences in purified genomic DNA samples. For statistical comparisons, a one-way analysis of variance and a Tukey’s test for post hoc analysis were carried out, and means ± SD are shown. Significance levels: *p ≤ 0.05, **p ≤ 0.01, ***p ≤ 0.001 versus control (untreated) cells
Mentions: Next, to assess the effect of vitamin D3 on the metastatic potential of germ line-derived tumor cells in vivo, we exposed A2780 human ovarian cancer (Fig. 5, panel a) and NTERA2 human teratocarcinoma cells (Fig. 5, panel b) to vitamin D3 before i.v. injection into immunodeficient mice. Incubation of tumor cells before injection with vitamin D3 decreased seeding efficiency of these cells into bone marrow, liver, and lung. This decrease in seeding efficiency can again be explained by the combined pro-apoptotic (Fig. 3), anti-proliferative (Fig. 4), anti-migratory (Fig. 2, panel a), and anti-adhesive (Fig. 2, panel b) effects of vitamin D3.Fig. 5

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