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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

Panel a 1,25-dihydroxyvitamin D3 inhibits migration of human and murine germline-derived cell lines. Transmigration of a human ovarian cancer cell line (A2780), a human teratocarcinoma cell line (NTERA-2), and a murine embryonal teratocarcinoma cell line (P19) through Transwell membranes (8-μm pore size) in response to 1,25-dihydroxyvitamin D3 at the indicated concentrations. Cells were rendered quiescent in 0.5 % BSA in culture medium overnight at 37 °C. The effects of 1,25-dihydroxyvitamin D3 on migration of all cell lines employed (6 × 104 cells/100 μL/insert) were also evaluated in parallel for migration in response to 10 % FBS and 0.5 % BSA plus vehicle as a positive and negative control, respectively. Twenty-four hours later, the migrated cells were stained and counted using an inverted microscope. Panel b 1,25-dihydroxyvitamin D3 interferes with the adhesiveness of human and murine germline-derived cell lines to fibronectin. Adhesion of the A2780 human ovarian cancer cell line, the NTERA-2 human teratocarcinoma cell line, and the P19 murine embryonal teratocarcinoma cell line to fibronectin-coated surfaces in response to 1,25-dihydroxyvitamin D3. After three hours of quiescence, cells (3000 cells/100 μL) were stimulated with 1,25-dihydroxyvitamin D3 at the indicated concentrations in medium with 0.5 % BSA for 5 min at 37 °C. After the non-adherent cells were removed by three consecutive washes with PBS, the number of adherent cells was measured by microscopic analysis. The effects of 1,25-dihydroxyvitamin D3 on adhesion of all cell lines employed were also evaluated for adhesion compared with stromal-derived factor 1 (300 ng/mL) and culture medium containing 0.5 % BSA plus vehicle as a positive and negative control, respectively. The negative control values are normalized to 100 %. Data are displayed as means ± SD, with a statistical significance *p ≤ 0.05 versus control (unstimulated) cells
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Fig2: Panel a 1,25-dihydroxyvitamin D3 inhibits migration of human and murine germline-derived cell lines. Transmigration of a human ovarian cancer cell line (A2780), a human teratocarcinoma cell line (NTERA-2), and a murine embryonal teratocarcinoma cell line (P19) through Transwell membranes (8-μm pore size) in response to 1,25-dihydroxyvitamin D3 at the indicated concentrations. Cells were rendered quiescent in 0.5 % BSA in culture medium overnight at 37 °C. The effects of 1,25-dihydroxyvitamin D3 on migration of all cell lines employed (6 × 104 cells/100 μL/insert) were also evaluated in parallel for migration in response to 10 % FBS and 0.5 % BSA plus vehicle as a positive and negative control, respectively. Twenty-four hours later, the migrated cells were stained and counted using an inverted microscope. Panel b 1,25-dihydroxyvitamin D3 interferes with the adhesiveness of human and murine germline-derived cell lines to fibronectin. Adhesion of the A2780 human ovarian cancer cell line, the NTERA-2 human teratocarcinoma cell line, and the P19 murine embryonal teratocarcinoma cell line to fibronectin-coated surfaces in response to 1,25-dihydroxyvitamin D3. After three hours of quiescence, cells (3000 cells/100 μL) were stimulated with 1,25-dihydroxyvitamin D3 at the indicated concentrations in medium with 0.5 % BSA for 5 min at 37 °C. After the non-adherent cells were removed by three consecutive washes with PBS, the number of adherent cells was measured by microscopic analysis. The effects of 1,25-dihydroxyvitamin D3 on adhesion of all cell lines employed were also evaluated for adhesion compared with stromal-derived factor 1 (300 ng/mL) and culture medium containing 0.5 % BSA plus vehicle as a positive and negative control, respectively. The negative control values are normalized to 100 %. Data are displayed as means ± SD, with a statistical significance *p ≤ 0.05 versus control (unstimulated) cells

Mentions: Based on observations from the literature that vitamin D3 has anti-metastatic properties [23, 24], we evaluated spontaneous migration of human and murine germline-derived tumor cells in response to vitamin D3 and observed a dose-dependent decrease in their spontaneous migration (Fig. 2, panel a) as well as adhesion to fibronectin (Fig. 2, panel b).Fig. 2


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)

Panel a 1,25-dihydroxyvitamin D3 inhibits migration of human and murine germline-derived cell lines. Transmigration of a human ovarian cancer cell line (A2780), a human teratocarcinoma cell line (NTERA-2), and a murine embryonal teratocarcinoma cell line (P19) through Transwell membranes (8-μm pore size) in response to 1,25-dihydroxyvitamin D3 at the indicated concentrations. Cells were rendered quiescent in 0.5 % BSA in culture medium overnight at 37 °C. The effects of 1,25-dihydroxyvitamin D3 on migration of all cell lines employed (6 × 104 cells/100 μL/insert) were also evaluated in parallel for migration in response to 10 % FBS and 0.5 % BSA plus vehicle as a positive and negative control, respectively. Twenty-four hours later, the migrated cells were stained and counted using an inverted microscope. Panel b 1,25-dihydroxyvitamin D3 interferes with the adhesiveness of human and murine germline-derived cell lines to fibronectin. Adhesion of the A2780 human ovarian cancer cell line, the NTERA-2 human teratocarcinoma cell line, and the P19 murine embryonal teratocarcinoma cell line to fibronectin-coated surfaces in response to 1,25-dihydroxyvitamin D3. After three hours of quiescence, cells (3000 cells/100 μL) were stimulated with 1,25-dihydroxyvitamin D3 at the indicated concentrations in medium with 0.5 % BSA for 5 min at 37 °C. After the non-adherent cells were removed by three consecutive washes with PBS, the number of adherent cells was measured by microscopic analysis. The effects of 1,25-dihydroxyvitamin D3 on adhesion of all cell lines employed were also evaluated for adhesion compared with stromal-derived factor 1 (300 ng/mL) and culture medium containing 0.5 % BSA plus vehicle as a positive and negative control, respectively. The negative control values are normalized to 100 %. Data are displayed as means ± SD, with a statistical significance *p ≤ 0.05 versus control (unstimulated) cells
© Copyright Policy - OpenAccess
Related In: Results  -  Collection

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getmorefigures.php?uid=PMC4835879&req=5

Fig2: Panel a 1,25-dihydroxyvitamin D3 inhibits migration of human and murine germline-derived cell lines. Transmigration of a human ovarian cancer cell line (A2780), a human teratocarcinoma cell line (NTERA-2), and a murine embryonal teratocarcinoma cell line (P19) through Transwell membranes (8-μm pore size) in response to 1,25-dihydroxyvitamin D3 at the indicated concentrations. Cells were rendered quiescent in 0.5 % BSA in culture medium overnight at 37 °C. The effects of 1,25-dihydroxyvitamin D3 on migration of all cell lines employed (6 × 104 cells/100 μL/insert) were also evaluated in parallel for migration in response to 10 % FBS and 0.5 % BSA plus vehicle as a positive and negative control, respectively. Twenty-four hours later, the migrated cells were stained and counted using an inverted microscope. Panel b 1,25-dihydroxyvitamin D3 interferes with the adhesiveness of human and murine germline-derived cell lines to fibronectin. Adhesion of the A2780 human ovarian cancer cell line, the NTERA-2 human teratocarcinoma cell line, and the P19 murine embryonal teratocarcinoma cell line to fibronectin-coated surfaces in response to 1,25-dihydroxyvitamin D3. After three hours of quiescence, cells (3000 cells/100 μL) were stimulated with 1,25-dihydroxyvitamin D3 at the indicated concentrations in medium with 0.5 % BSA for 5 min at 37 °C. After the non-adherent cells were removed by three consecutive washes with PBS, the number of adherent cells was measured by microscopic analysis. The effects of 1,25-dihydroxyvitamin D3 on adhesion of all cell lines employed were also evaluated for adhesion compared with stromal-derived factor 1 (300 ng/mL) and culture medium containing 0.5 % BSA plus vehicle as a positive and negative control, respectively. The negative control values are normalized to 100 %. Data are displayed as means ± SD, with a statistical significance *p ≤ 0.05 versus control (unstimulated) cells
Mentions: Based on observations from the literature that vitamin D3 has anti-metastatic properties [23, 24], we evaluated spontaneous migration of human and murine germline-derived tumor cells in response to vitamin D3 and observed a dose-dependent decrease in their spontaneous migration (Fig. 2, panel a) as well as adhesion to fibronectin (Fig. 2, panel b).Fig. 2

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