2005 Fiscal Year Final Research Report Summary
Research for molecular mechanisms of lymphangiogenesis and lymph node metastasis
| Project/Area Number |
16390378
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Digestive surgery
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| Research Institution | Kyoto University |
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Principal Investigator |
KUBO Hajime Kyoto University, Graduate School of Medicine, Associate Professor, 医学研究科, 科学技術振興助教授 (50362520)
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| Project Period (FY) |
2004 – 2005
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| Keywords | Lymphangiogensis / Lymph node metastasis / ES cells / tumor suppressor gene / RNA editing |
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| Research Abstract |
1.The expression of lymphatic marker, podoplanin by cancer were associated with the frequency of lymph node metastasis.
We established novel anti-human podoplanin antibodies, and found the expression by several cancer cells using tissue microarrays. We also found that podoplanin was the specific marker for mesothelioma.
2.Homeobox gene, prox1 as a novel tumor suppressor gene.
We found that there was a significant correlation between prox1 expression and the differentiation scores of the tumors. Subsequently, we also showed that low expression of prox1 in tumors was closely associated with a poor prognosis. The specific knockdown of prox1 by RNA interference strongly accelerated in vitro cell growth, while the over-expression of prox1 greatly suppressed the growth.
3.Two populations of Thy1-positive mesenchymal cells regulate the in vitro maturation of hepatic progenitor cells
We determined that the mucin-type transmembrane glycoprotein gp38 could distinguish the cuboidal cells from the spin
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dle cells by immunocytochemistry. In vitro maturation of hepatic progenitor cells promoted by gp38-positive cells may be opposed by an inhibitory effect of gp38-negative cells, which likely maintain the immature, proliferative state of CD49f-positive cells.
4.Differentiation of lymphatic endothelial cells from Embryonic Stem cells on OP9 stromal cells
VEGFR-2^+ cells derived from ES cells differentiated into LECs at day3 on OP9 stromal cells defined by the expression of prox1, VEGFR-3 and another lymphatic marker podoplanin. VEGFR-2^+ cells gave rise to LYVE-1^+ embryonic ECs, which were negative for prox1 on day1 but turned to prox1^+ LECs by day3. VEGFR3-Fc or Tie2-Fc, sequestering VEGF-C or angiopoietin 1 (Ang1), suppressed colony formation of LECs on OP9 cells. However, addition of VEGF-C and Ang1 in combination with VEGF to the culture of VEGFR-2^+ cells on collagen-coated dishes failed to induce LECs. LEC inducing activity of OP9 cells was fully reproduced on PFA-fixed OP9 cells with the conditioned medium. Less
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