Inflammatory breast cancer: Vasculogenic mimicry and its hemodynamics of an inflammatory breast cancer xenograft model

Abstract

136 EC = endothelial cell; IBC = inflammatory breast cancer; MRA = magnetic resonance angiography; VEGF = vascular endothelial growth factor; VM = vasculogenic mimicry. Breast Cancer Research Vol 5 No 3 Shirakawa et al. IntroductionGrowth, proliferation, and metastasis of breast cancer, and of most other tumors, have been thought to be angiogenesis-dependent processes [1]. However, a non-angiogenesis-dependent pathway, in which tumors can feed themselves using alternative pathways, has also been reported [2][3][4][5][6][7][8][9][10][11][12]. Previously, we and others described the presence of vasculogenic mimicry (VM, a condition in which tumors [inflammatory breast cancer {IBC} and melanoma] feed themselves using alternative pathways without the participation of endothelial cells [ECs]) in the tumor-bearing state. In the present study, we established a new human IBC xenograft (WIBC-9) in BALB/c nude mice and investigated the hemodynamics of VM and angiogenesis of IBC, using WIBC-9 xenografts and dynamic micro-magnetic resonance angiography (micro-MRA) analysis. The unique patterns characteristic of VM and its hemodynamics provide a framework for the design of non-invasive imaging techniques for detecting IBC and its metastases. Method Morphological and chromosomal analysisThe animal protocols for all experiments were approved by the Animal Use Committee of the National Cancer Center. Hematoxylin-eosin and Giemsa staining of paraffin-embedded specimens were performed, as were electron microscopic examinations following a conventional method. For karyotype studies of the xenograft, the Giemsa G banding method was performed after 6 and 12 passages. Dynamic micro-MRA with an intravascular contrast agentWe performed dynamic micro-MRA analysis, using our newly developed intravascular macromolecular contrast agent for magnetic resonance imaging, which consistently showed no significant leakage through the vascular wall AbstractWe recently established a new human inflammatory breast cancer (IBC) xenograft (WIBC-9) originating from a patient with IBC. The original tumor and WIBC-9 revealed invasive ductal carcinoma with a hypervascular structure of solid nests and marked lymphatic permeation in the overlying dermis. In the central part of the solid nests, vasculogenic mimicry, which showed an absence of endothelial cells, was observed. Comparison of WIBC-9 with an established non-IBC xenograft (MC-5), using time-course dynamic micro-magnetic resonance angiography analysis (with a newly developed intravascular macromolecular contrast agent for magnetic resonance imaging) demonstrated that the WIBC-9 tumor had blood flow and a vascular mimicry-angiogenesis junction.

The Clinical Significance of Tumor Cell-Lined Vasculature in Ovarian Carcinoma: Implications for Anti-Vasculogenic Therapy

“…Shirakawa and colleagues, using in vivo models of breast carcinoma, have demonstrated that aggressive breast tumors portray vasculogenic mimicry (without endothelial cells or central necrosis) that connects to angiogenic vessels at the tumor periphery. 5 In contrast, …”

“…We and others have proposed that tumors, including ovarian carcinoma, may develop vascularization through angiogenesis as well as alternative pathways such as vasculogenic mimicry and mosaic vessels. [2][3][4][5][6] We have previously demonstrated that aggressive ovarian cancer cells, but not normal ovarian surface epithelial cells, are able to form vasculogenic-like networks in three-dimensional cultures, with concomitant expression of vascular-associated cell markers. 2 In addition, we have demonstrated that tumor cell-lined vasculature can be detected in aggressive cancers in vivo.…”

Immunohistochemistry in the evaluation of neovascularization in tumor xenografts

“…Recent studies also have shown that some aggressive tumor cells can generate vessel-like channels, i.e., vasculogenic mimicry in the absence of endothelial cells (Shirakawa et al 2002, Su et al 2007), thus providing another pathway for tumor perfusion independent of angiogenesis (Folberg et al 2000). Su et al (2007) reported that the human ovarian cancer cell line SKOV3.ip1 may express some endothelium-specific markers after vasculogenic mimicry in vivo.…”

Vasculogenic mimicry is associated with high tumor grade, invasion and metastasis, and short survival in patients with hepatocellular carcinoma

“…VM has been reported in inflammatory breast cancer (6), prostate cancer (7), invasive ovarian cancer (8), sarcoma (9), and astrocytoma (10). VM is also involved in the invasion and metastasis of malignant tumors (6,7,11) and has been associated with poor prognosis in melanoma and sarcomas (8,9).…”