Preexisting lymphatic endothelium but not endothelial progenitor cells are essential for tumor lymphangiogenesis and lymphatic metastasis

Preexisting lymphatic endothelium but not endothelial progenitor cells are essential for tumor lymphangiogenesis and lymphatic metastasis
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DOI:
10.1158/0008-5472.can-04-0088
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发表时间:
2004-06-01
期刊:
影响因子:
11.2
通讯作者:
Alitalo, K
Alitalo, K
中科院分区:
医学1区
文献类型:
--
作者:
He, YL;Rajantie, I;Alitalo, K

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内皮祖细胞已被证明有助于血管生成在各种肿瘤模型。在这里,我们研究了骨髓来源的内皮祖细胞和预先存在的淋巴管对肿瘤淋巴管生成的相对贡献。在肿瘤或血管内皮生长因子c诱导的淋巴管生成过程中,我们没有发现遗传标记的bm来源细胞在淋巴管中显著结合。肿瘤淋巴管生成的程度与肿瘤周围淋巴管密度相关,尽管肿瘤淋巴管生成,但在淋巴网发育不全的基因靶向血管内皮生长因子C+/-小鼠中未能发生淋巴转移。我们的数据表明,在肿瘤淋巴管形成和癌细胞通过淋巴管传播的过程中,新形成的淋巴管从预先存在的局部淋巴管网络中萌芽,几乎没有合并来自脑梗死的内皮祖细胞。
Endothelial progenitor cells have been shown to contribute to angiogenesis in various tumor models. Here, we have studied the relative contributions of bone marrow (BM)-derived endothelial progenitors and pre-existing lymphatic vessels to tumor lymphangiogenesis. We did not find significant incorporation of genetically marked BM-derived cells in lymphatic vessels during tumor- or vascular endothelial growth factor C-induced lymphangiogenesis. The degree of tumor lymphangiogenesis correlated with lymphatic vessel density in the peritumoral area, and despite tumor lymphangiogenesis, lymphatic metastasis failed to occur in gene-targeted vascular endothelial growth factor C+/- mice that have hypoplasia of the lymphatic network. Our data demonstrate that during tumor lymphangiogenesis and cancer cell dissemination via the lymphatics, the newly formed lymphatic vessels sprout from the pre-existing local lymphatic network with little if any incorporation of BM-derived endothelial progenitor cells.