Molecular determinants of ovarian cancer plasticity
Molecular determinants of ovarian cancer plasticity
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DOI：
10.1016/s0002-9440(10)64079-5
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发表时间：
2001-04-01
影响因子：
6
通讯作者：
Hendrix, MJC
中科院分区：
文献类型：
--
作者：
Sood, AK;Seftor, EA;Hendrix, MJC
在发育过程中，初级血管网络的形成和重塑通过血管生成和血管生成发生。最近，“血管生成拟态”一词被我们的实验室和合作者用来反映侵袭性但非侵袭性黑色素瘤细胞的胚胎样能力，在三维培养中形成围绕肿瘤细胞球体的富含基质的网络(包含通道)的模式，伴随着它们的血管细胞标志物的表达。在大多数患者中，卵巢癌通常被诊断为晚期疾病，当腹膜腔内已经建立了广泛的转移时，在本研究中，我们探讨了侵袭性卵巢癌细胞与正常细胞相比，是否可以通过其可塑性来进行分子血管生成拟态。结果显示，在含有Matrigel或I型胶原的三维培养中，侵袭性卵巢癌细胞(而不是正常卵巢表面上皮细胞)形成含有实心和中空基质通道的花纹网络，在没有内皮细胞或成纤维细胞的情况下，免疫组织化学分析显示基质金属蛋白酶-1、-2、-9和MT1-MMP散在这些网络中定位，并被基质金属蛋白酶抑制剂抑制。此外，核糖核酸酶保护实验显示侵袭性卵巢癌细胞表达多种血管细胞相关标志。在高分期、高级别卵巢癌患者的肿瘤切片中，含有红细胞的通道中有7%至10%被肿瘤细胞排列。相比之下，良性肿瘤和低期癌症的所有血管区域都是内皮细胞衬里的。这些结果可能为考虑基于侵袭性肿瘤细胞分子血管模拟的卵巢癌诊断和治疗策略提供新的见解和分子标志物。
During development, the formation and remodeling of primary vascular networks occurs by vasculogenesis and angiogenesis. Recently, the term "vasculo-genic mimicry" has been used by our laboratory and collaborators to reflect the embryonic-like ability of aggressive, but not nonaggressive, melanoma tumor cells to form a pattern of matrix-rich networks (containing channels) surrounding spheroids of tumor cells in three-dimensional culture, concomitant with their expression of vascular cell markers. Ovarian cancer is usually diagnosed as advanced stage disease in most patients when widespread metastases have already been established within the peritoneal cavity, in this study, we explored whether invasive ovarian carcinoma cells could engage in molecular vasculogenic mimicry reflected by their plasticity, compared with their normal cell counterparts. The data revealed that the invasive ovarian cancer cells, but not normal ovarian surface epithelial cells, formed patterned networks containing solid and hollow matrix channels when grown in three-dimensional cultures containing Matrigel or type I collagen, in the absence of endothelial cells or fibroblasts, Immunohistochemical analysis showed that matrix metalloproteinases (MMP)-1, -2, and -9, and MT1-MMP were discretely localized to these networks, and the formation of the networks was inhibited by treatment with MMP inhibitors, Furthermore, the RNase protection assay revealed the expression of multiple vascular cell-associated markers by the Invasive ovarian cancer cells. In patient tumor sections from high-stage, high-grade ovarian cancers, 7 to 10% of channels containing red blood cells were lined by tumor cells. By comparison, all vascular areas in benign tumors and low-stage cancers were endothelial lined. These results may offer new insights and molecular markers for consideration in ovarian cancer diagnosis and treatment strategies based on molecular vascular mimicry by aggressive tumor cells.