Involvement of the collagen I-binding motif in the anti-angiogenic activity of pigment epithelium-derived factor
Involvement of the collagen I-binding motif in the anti-angiogenic activity of pigment epithelium-derived factor
复制标题
DOI：
10.1016/j.bbrc.2005.07.140
复制
发表时间：
2005-09-30
影响因子：
3.1
通讯作者：
Morita, I
中科院分区：
文献类型：
--
作者：
Hosomichi, J;Yasui, N;Morita, I
色素上皮衍生因子（PEDF）是年龄相关性黄斑变性和肿瘤中最有效的内源性血管生成抑制剂。然而，PEDF抗血管生成活性的分子机制尚不清楚。PEDF在体外与细胞外基质（ECM）相互作用。在这里，我们研究了ECM相互作用的基序可能参与PEDF的抗血管生成活性。转染PEDF后，培养的HeLa细胞的生长速率不受影响，说明PEDF不直接抑制肿瘤细胞的生长。在肿瘤异种移植物中，过表达野生型PEDF显著抑制肿瘤生长，而PEDF的胶原i结合位点突变体（Col-mut PEDF）不抑制肿瘤生长。PEDF的肝素结合位点突变体（Hep-mut PEDF）抑制肿瘤生长。组织学分析表明，与载体PEDF或Col-mut PEDF相比，PEDF或Hep-mut PEDF的微血管密度和面积均受到抑制。我们的数据表明，PEDF通过其抗血管生成活性抑制肿瘤生长，PEDF的胶原i结合基序参与了生物活性。(C) 2005爱思唯尔公司版权所有。
Pigment epithelium-derived factor (PEDF) is the most potent endogenous inhibitor of angiogenesis in age-related macular degeneration and tumors. However, the molecular mechanism of the anti-angiogenic activity of PEDF is poorly understood. PEDF interacts with the extracellular matrix (ECM) in vitro. Here, we investigated the possible involvement of the motif for ECM interaction in the anti-angiogenic activity of PEDF. The growth rates of HeLa cells in culture were not affected by transfection of PEDF, indicating that PEDF did not suppress tumor cell growth directly. In tumor xenografts, the overexpression of wild-type PEDF significantly suppressed tumor growth, whereas a mutant of the collagen I-binding site of PEDF (Col-mut PEDF) did not inhibit tumor growth. A mutant of the heparin-binding site of PEDF (Hep-mut PEDF) suppressed tumor growth. Histological analysis showed that the density and area of microvasculatures in either PEDF or Hep-mut PEDF were suppressed when compared with those in either vector or Col-mut PEDF. Our data indicate that PEDF inhibits tumor growth via its anti-angiogenic activity, and the collagen I-binding motif of PEDF is involved in the biological activity. (C) 2005 Elsevier Inc. All rights reserved.