Abstract
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.
Highlights
Human inflammatory breast cancer (IBC) and canine inflammatory mammary cancer (IMC) are the most lethal mammary cancers
VEGF-A is an angiogenic marker that is overexpressed in IBC/IMC and it is present in normal endothelial cells and in neoplastic cells [10, 12]
The aims of this study were to analyze by transmission and scanning electron microscopy (TEM and Scanning Electron Microscope (SEM)), the human IBC cell line (SUM149) and the canine IMC cell line (IPC-366) in adherent (2D) and non-adherent (3D) conditions in order to compare the morphological characteristics of both cell lines for the better understanding of their biology and to further support the IPC-366 cell line as a good comparative model for human IBC
Summary
Human 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. Human inflammatory breast cancer (IBC) and canine inflammatory mammary cancer (IMC) are the most aggressive mammary neoplasms and are associated to poor prognosis in both species [1,2,3,4,5]. The criterium for histological diagnosis for IBC and IMC is the enormous neoplastic embolization of dermal lymphatic vessels which blockade lymphatic drainage originating the Characteristically, exacerbated angiogenesis, lymphangiogenesis, lymphangiotropism and vasculogenic mimicry (VM) are found in IBC and IMC [5, 9, 10, 12, 13]. According to our previous study, both cell lines overexpress VEGF-A and contributes to the exacerbated angiogenesis [15]. Multiple studies have used angiogenesis inhibitors as adjuvant therapy and they have failed to provide significant benefits to patients [18]
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