Epithelial-mesenchymal transition of ovarian tumor cells induces an angiogenic monocyte cell population
Epithelial-mesenchymal transition of ovarian tumor cells induces an angiogenic monocyte cell population
复制标题
DOI：
10.1016/j.yexcr.2009.06.010
复制
发表时间：
2009-10-15
影响因子：
3.7
通讯作者：
Bussolati, Benedetta
中科院分区：
文献类型：
--
作者：
Collino, Federica;Revelli, Alberto;Bussolati, Benedetta
血管生成，或能够分化为内皮样细胞的前体细胞的招募，可能对肿瘤中新生血管的形成做出重要贡献。然而，涉及血管生成过程的因素，特别是肿瘤细胞上皮-间充质转化的作用尚未被研究。我们发现CD14(+)/KDR(+)在未分化的卵巢肿瘤中有血管生成的单核细胞群，在相应的肿瘤转移中显著增加。在体外，表达间充质表型的原代卵巢肿瘤细胞的条件培养液可诱导单核细胞分化为CD14(+)/KDR(+)细胞。相反，卵巢肿瘤细胞株SKOV3表达上皮性表型，不能刺激单核细胞分化为CD14(+)/KDR(+)细胞。当在SKOV3中诱导上皮-间充质转化时，它们获得了这种分化能力。此外，间充质转化后，SKOV3的多核营养因子表达增加，反之，其阻断显著减少单核细胞的分化。获得的CD14(+)/KDR(+)细胞群在体外表达内皮细胞标志物，促进内皮细胞形成毛细血管样结构，促进卵巢肿瘤细胞迁移。综上所述，卵巢肿瘤细胞上皮-间充质转化诱导单核细胞向促血管生成CD14(+)/KDR(+)细胞分化，可能为卵巢癌提供有利于血管生成和转移的肿瘤微环境。(C)2009 Elsevier Inc.保留所有权利。
Vasculogenesis, or recruitment of progenitors able to differentiate into endothelial-like cells, may provide an important contribution to neovessel formation in tumors. However, the factors involved in the vasculogenic process and in particular the role of the epithelial-mesenchymal transition of tumor cells have not yet been investigated. We found a CD14(+)/KDR(+) angiogenic monocyte population in undifferentiated ovarian tumors, significantly increased in the corresponding tumor metastasis. In vitro, monocyte differentiation into CD14(+)/KDR(+) cells was induced by conditioned media from the primary ovarian tumor cells expressing a mesenchymal phenotype. In contrast, the ovarian tumor cell line SKOV3 expressing an epithelial phenotype was unable to stimulate the differentiation of monocytes into CD14(+)/KDR(+) cells. When an epithelial-mesenchymal transition was induced in SKOV3, they acquired this differentiative ability. Moreover, after mesenchymal transition pleiotrophin expression by SKOV3 was increased and conversely its blockade significantly reduced monocyte differentiation. The obtained CD14(+)/KDR(+) cell population showed the expression of endothelial markers, increased the formation of capillary-like structures by endothelial cells and promoted the migration of ovarian tumor cells in vitro. In conclusion, we showed that the epithelial-mesenchymal transition of ovarian tumor cells induced differentiation of monocytes into the pro-angiogenic CD14(+)/KDR(+) population and thus it may provide a tumor microenvironment that favours vasculogenesis and metastatization of the ovarian cancer. (C) 2009 Elsevier Inc. All rights reserved.