Vasculogenic mimicry-associated ultrastructural findings in human and canine inflammatory breast cancer cell lines
Vasculogenic mimicry-associated ultrastructural findings in human and canine inflammatory breast cancer cell lines
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DOI：
10.1186/s12885-019-5955-z
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发表时间：
2019-07-30
期刊：
影响因子：
3.8
通讯作者：
Pena, Laura
中科院分区：
文献类型：
--
作者：
Barreno, Lucia;Caceres, Sara;Pena, Laura
背景人类炎症性乳腺癌（IBC）和犬炎症性乳腺癌（IMC）是最致命的乳腺癌。血管生成加剧和血管生成拟态（VM）的存在是这些肿瘤的标志。有关乳腺细胞系 VM 和超微结构特征的信息很少。方法在本研究中，通过透射和扫描电子显微镜（分别为 TEM 和 SEM）对贴壁 (2D) 和非贴壁 (3D)（乳腺球、癌症干细胞）条件下的 IBC 细胞系 SUM149 和 IMC 细胞系 IPC-366 进行分析。结果 TEM 显示圆形至椭圆形细胞，表面有微绒毛，细胞数量较多。过氧化物酶体与脂滴和一些细胞外衍生的囊泡紧密相连。 TEM 和 SEM 乳腺球显示细胞群与中央腔（类似于乳腺腺泡）聚集在一起。细胞连接紧密连接，小带粘附。通过SEM观察到两种细胞形态：球形和扁平细胞。有证据表明内皮样细胞（ELC）是这种疾病的特征，显示出多个或独特的细胞质空白空间。 ELC 在 3D 培养条件下比在 2D 培养条件下更常见，并且含有 Weibel-Palade 细胞质体，这是内皮细胞独有的结构。结论 IPC-366 和 SUM-149 两种细胞系具有共同的超微结构特征，进一步支持犬 IMC 作为人类疾病的模型。据我们所知，这是第一项证明培养的癌症干细胞从癌上皮细胞系向内皮样细胞形态分化的研究，从超微结构的角度证实了血管生成拟态现象。
BackgroundHuman inflammatory breast cancer (IBC) and canine inflammatory mammary cancer (IMC) are the most lethal mammary cancers. An exacerbated angiogenesis and the existence of vasculogenic mimicry (VM) are hallmarks of these tumors. The information regarding VM and ultrastructural characteristics of mammary cell lines is scant.MethodsIn this study, IBC cell line SUM149 and IMC cell line IPC-366 in adherent (2D) and non-adherent (3D) (mammospheres, cancer stem cells) conditions were analyzed by transmission and scanning electron microscopy (TEM and SEM, respectively).ResultsThe TEM revealed round to oval shape cells with microvilli on the surface, high numbers of peroxisomes in close apposition to lipid droplets and some extracellular derived vesicles. The TEM and the SEM mammospheres revealed group of cells clumping together with a central lumen (resembling a mammary acini). The cells joint are tight junctions and zonula adherens. By SEM two cell morphologies were observed: spherical and flattened cells. There was evidence endothelial-like cells (ELCs), which is characteristic for this disease, showing several or unique cytoplasmic empty space. ELCs were more frequent in 3D than in 2D culture conditions and contained Weibel-Palade cytoplasmic bodies, which are exclusive structures of endothelial cells.ConclusionsBoth cell lines, IPC-366 and SUM-149, shared ultrastructural characteristics, further supporting canine IMC as a model for the human disease. To the best of our knowledge, this is the first study that demonstrate the morphological differentiation of cultured cancer stem cells from cancer epithelial cell lines into endothelial-like cells, confirming the vasculogenic mimicry phenomenon from an ultrastructural point of view.