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논문 기본 정보
- 자료유형
- 학술저널
- 저자정보
- 발행연도
- 2017.1
- 수록면
- 1 - 8 (8page)
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Tumor growth is governed by the coordinated action of various types of cells that are present in the tumor environment. Fibroblasts, which constitute a major fraction of the stroma, participate actively in various signaling events and regulate tumor development and metastasis. The Hedgehog (Hh) pathway plays an important role in promoting tumor malignancy via fibroblasts; however, the role of hedgehog interacting protein (hhip; inhibitor of Hh pathway) in tumor growth is poorly understood. Here we implanted B16F10 tumors in hhip+/ − mice to study the tumor growth characteristics and the vascular phenotype. Furthermore, the mechanism involved in the observed phenomena was explored to reveal the role of hhip in tumor growth. The tumors that were implanted in hhip+/ − mice exhibited accelerated growth and increased tumor angiogenesis. Although we observed a decrease in hypoxia, blood vessels still had abnormal phenotype. We found that increased Hh signaling in tumor fibroblasts induced a high expression of vascular endothelial growth factor (VEGF), which subsequently resulted in an increased proliferation of endothelial cells. Thus, the heterozygous knockdown of hhip in mice could affect Hh signaling in tumor fibroblasts, which could cause the increased production of the growth factor VEGF. This signaling, via a paracrine effect on endothelial cells, increased tumor vascular density.
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참고문헌 (24)
참고문헌 신청
Alphonso A / 2009 / Stromal cells and integrins : conforming to the needs of the tumor microenvironment / Neoplasia 11 : 1264 ~ 1271
Augsten M / 2014 / Cancer-associated fibroblasts as another polarized cell type of the tumor microenvironment / Front Oncol 4 : 62 ~
Chen W / 2011 / Canonical hedgehog signaling augments tumor angiogenesis by induction of VEGF-A in stromal perivascular cells / Proc Natl Acad Sci USA 108 : 9589 ~ 9594
Chuang PT / 1999 / Vertebrate Hedgehog signalling modulated by induction of a Hedgehog-binding protein / Nature 397 : 617 ~ 621
Chuang PT / 2003 / Feedback control of mammalian Hedgehog signaling by the Hedgehog-binding protein, Hip1, modulates Fgf signaling during branching morphogenesis of the lung
Augsten M / 2014 / Cancer-associated fibroblasts as another polarized cell type of the tumor microenvironment / Front Oncol 4 : 62 ~
Chen W / 2011 / Canonical hedgehog signaling augments tumor angiogenesis by induction of VEGF-A in stromal perivascular cells / Proc Natl Acad Sci USA 108 : 9589 ~ 9594
Chuang PT / 1999 / Vertebrate Hedgehog signalling modulated by induction of a Hedgehog-binding protein / Nature 397 : 617 ~ 621
Chuang PT / 2003 / Feedback control of mammalian Hedgehog signaling by the Hedgehog-binding protein, Hip1, modulates Fgf signaling during branching morphogenesis of the lung
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