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Indoleamine 2,3-dioxygenase promotes peritoneal metastasis of ovarian cancer by inducing an immunosuppressive environment.

Tanizaki Y, Kobayashi A, Toujima S, Shiro M, Mizoguchi M, Mabuchi Y, Yagi S, Minami S, Takikawa O, Ino K - Cancer Sci. (2014)

Bottom Line: This tumor-progressive effect was coincident with significantly reduced numbers of CD8(+) T cells and natural killer cells within tumors as well as increased levels of transforming growth factor-β and interleukin-10 in ascites.Finally, treatment with the IDO inhibitor 1-methyl-tryptophan significantly suppressed tumor dissemination and ascites with reduced transforming growth factor-β secretion.These findings showed that tumor-derived IDO promotes the peritoneal dissemination of ovarian cancer through suppression of tumor-infiltrating effector T cell and natural killer cell recruitment and reciprocal enhancement of immunosuppressive cytokines in ascites, creating an immunotolerogenic environment within the peritoneal cavity.

View Article: PubMed Central - PubMed

Affiliation: Department of Obstetrics and Gynecology, Wakayama Medical University, Wakayama, Japan.

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Effects of transforming growth factor-β (TGF-β) and interleukin-10 (IL-10) on in vitro cell migratory potential of HM-1-parental, control vector-transfected (HM-1-mock), and indoleamine 2,3-dioxygenase-overexpressing (HM-1-IDO) murine ovarian carcinoma OV2944-HM-1 cells. The cell migratory activity in the presence or absence of 1 ng/mL TGF-β or IL-10 was evaluated by wound healing assay after 24 h. Mean ± SD from three independent experiments are shown. *P < 0.05, TGF-β (+) versus control.
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fig05: Effects of transforming growth factor-β (TGF-β) and interleukin-10 (IL-10) on in vitro cell migratory potential of HM-1-parental, control vector-transfected (HM-1-mock), and indoleamine 2,3-dioxygenase-overexpressing (HM-1-IDO) murine ovarian carcinoma OV2944-HM-1 cells. The cell migratory activity in the presence or absence of 1 ng/mL TGF-β or IL-10 was evaluated by wound healing assay after 24 h. Mean ± SD from three independent experiments are shown. *P < 0.05, TGF-β (+) versus control.

Mentions: Because the levels of TGF-β and IL-10 in the ascites were significantly higher in HM-1-IDO-transplanted mice than in HM-1-mock-transplanted ones, we examined whether TGF-β and IL-10 could affect the proliferation and migration of HM-1 cells in vitro. Transforming growth factor-β enhanced the cell migratory activity in HM-1-parental, HM-1-mock, and HM-1-IDO cells to similar extents, whereas IL-10 had no significant effects on cell migration (Fig. 5). Neither TGF-β nor IL-10 showed significant effects on the proliferative activity of these cells (data not shown).


Indoleamine 2,3-dioxygenase promotes peritoneal metastasis of ovarian cancer by inducing an immunosuppressive environment.

Tanizaki Y, Kobayashi A, Toujima S, Shiro M, Mizoguchi M, Mabuchi Y, Yagi S, Minami S, Takikawa O, Ino K - Cancer Sci. (2014)

Effects of transforming growth factor-β (TGF-β) and interleukin-10 (IL-10) on in vitro cell migratory potential of HM-1-parental, control vector-transfected (HM-1-mock), and indoleamine 2,3-dioxygenase-overexpressing (HM-1-IDO) murine ovarian carcinoma OV2944-HM-1 cells. The cell migratory activity in the presence or absence of 1 ng/mL TGF-β or IL-10 was evaluated by wound healing assay after 24 h. Mean ± SD from three independent experiments are shown. *P < 0.05, TGF-β (+) versus control.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4317851&req=5

fig05: Effects of transforming growth factor-β (TGF-β) and interleukin-10 (IL-10) on in vitro cell migratory potential of HM-1-parental, control vector-transfected (HM-1-mock), and indoleamine 2,3-dioxygenase-overexpressing (HM-1-IDO) murine ovarian carcinoma OV2944-HM-1 cells. The cell migratory activity in the presence or absence of 1 ng/mL TGF-β or IL-10 was evaluated by wound healing assay after 24 h. Mean ± SD from three independent experiments are shown. *P < 0.05, TGF-β (+) versus control.
Mentions: Because the levels of TGF-β and IL-10 in the ascites were significantly higher in HM-1-IDO-transplanted mice than in HM-1-mock-transplanted ones, we examined whether TGF-β and IL-10 could affect the proliferation and migration of HM-1 cells in vitro. Transforming growth factor-β enhanced the cell migratory activity in HM-1-parental, HM-1-mock, and HM-1-IDO cells to similar extents, whereas IL-10 had no significant effects on cell migration (Fig. 5). Neither TGF-β nor IL-10 showed significant effects on the proliferative activity of these cells (data not shown).

Bottom Line: This tumor-progressive effect was coincident with significantly reduced numbers of CD8(+) T cells and natural killer cells within tumors as well as increased levels of transforming growth factor-β and interleukin-10 in ascites.Finally, treatment with the IDO inhibitor 1-methyl-tryptophan significantly suppressed tumor dissemination and ascites with reduced transforming growth factor-β secretion.These findings showed that tumor-derived IDO promotes the peritoneal dissemination of ovarian cancer through suppression of tumor-infiltrating effector T cell and natural killer cell recruitment and reciprocal enhancement of immunosuppressive cytokines in ascites, creating an immunotolerogenic environment within the peritoneal cavity.

View Article: PubMed Central - PubMed

Affiliation: Department of Obstetrics and Gynecology, Wakayama Medical University, Wakayama, Japan.

Show MeSH
Related in: MedlinePlus