title: Hemodynamics in vasculogenic mimicry and angiogenesis of inflammatory breast cancer xenograft.
abstract: In the present study, we examined hemodynamics in vasculogenic mimicry (VM) and angiogenesis of inflammatory breast cancer (IBC) xenografts (WIBC-9), having previously reported on the unique histological features and molecular basis of these processes (K. Shirakawa et al., Cancer Res., 61: 445-451, 2001). Histologically, the WIBC-9 xenografts exhibited invasive ductal carcinoma with a hypervascular structure (angiogenesis) in the tumor margin and VM without endothelial cells, central necrosis, or fibrosis in the tumor center. Results of molecular analysis indicated that WIBC-9 had a vasculogenic phenotype, including expression of Flt-1 and Tie-2. Comparison of WIBC-9 with an established non-IBC xenograft (MC-5), using time-coursed dynamic micromagnetic resonance angiography analysis (with our newly developed intravascular macromolecular magnetic resonance imaging contrast agent), electromicroscopy, and immunohistochemistry, demonstrated blood flow and a VM-angiogenesis junction in the central area of the WIBC-9 tumor. It has previously been considered impossible to prove a connection between VM and angiogenesis using angiography, because there are no intravascular macromolecular magnetic resonance imaging contrast agents that do not exhibit significant leakage through the vascular wall. In the present study, laser-captured microdissection was performed in regions of WIBC-9 tumors that exhibited VM without endothelial cells, central necrosis, or fibrosis, revealing expression of human-Flt-1 and human-Tie2 and the absence of human-CD31, human-endothelin B receptor, and human-thrombin receptor. These facts led us to hypothesize that the VM of WIBC-9 involves hemodynamics that serve to feed WIBC-9 cells, and this in turn suggests a connection between VM and angiogenesis.
authors.affiliation: Pharmacology Division, National Cancer Center Research Institute, Tokyo 104-0045, Japan.
authors.forename: Kazuo
authors.initials: K
authors.lastname: Shirakawa
authors.forename: Hisataka
authors.initials: H
authors.lastname: Kobayashi
authors.forename: Yuji
authors.initials: Y
authors.lastname: Heike
authors.forename: Satomi
authors.initials: S
authors.lastname: Kawamoto
authors.forename: Martin W
authors.initials: MW
authors.lastname: Brechbiel
authors.forename: Fujio
authors.initials: F
authors.lastname: Kasumi
authors.forename: Toshihiko
authors.initials: T
authors.lastname: Iwanaga
authors.forename: Fumio
authors.initials: F
authors.lastname: Konishi
authors.forename: Masaaki
authors.initials: M
authors.lastname: Terada
authors.forename: Hiro
authors.initials: H
authors.lastname: Wakasugi
mesh_terms: D000818:Animals; D001943:Breast Neoplasms / Q000098:blood supply* / Q000473:pathology / Q000503:physiopathology; D018270:Carcinoma, Ductal, Breast / Q000098:blood supply* / Q000473:pathology / Q000503:physiopathology; D003287:Contrast Media; D005260:Female; D006439:Hemodynamics / Q000502:physiology; D006801:Humans; D018810:Magnetic Resonance Angiography; D051379:Mice; D009368:Neoplasm Transplantation; D009389:Neovascularization, Pathologic / Q000503:physiopathology*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014183:Transplantation, Heterologous
chemical_list: D003287:Contrast Media