Induction of vasculogenesis in breast cancer models

Abstract

Recently, there have been reports of postnatal vasculogenesis in cases of ischaemia models. The aim of the present study is to provide evidence of postnatal vasculogenesis in breast-cancer -bearing mice. Based on cell surface antigen expression, we isolated endothelial precursor cells from bone marrow, peripheral blood and tumour-infiltrating cells from mice that had received six human breast cancer xenografts. In all three areas (bone marrow, peripheral blood and tumour-infiltrating cells), endothelial precursor cell population was elevated in all transplanted mice. Differentiation and migration activities of endothelial precursor cells were measured by comparing levels of the endothelial precursor cell maturation markers Flk-1, Flt-1, Tie2, VE-cadherin and CD31 among these three areas. The endothelial precursor cell population was 14% or greater in the gated lymphocyte-size fraction of the inflammatory breast cancer xenograft named WIBC-9, which exhibits a hypervascular structure and de novo formation of vascular channels, namely vasculogenic mimicry (Shirakawa et al, 2001). In vitro, bone marrow-derived endothelial precursor cells from four human breast cancer xenografts proliferated and formed multiple clusters of spindle-shaped attaching cells on a vitronectin-coated dish. The attaching cells, which incorporated DiI-labelled acetylated low-density lipoprotein (DiI-acLDL) and were negative for Mac-1. The putative bone marrow derived endothelial precursor cell subset, which was double positive of CD34 and Flk-1, and comparative bone marrow derived CD34 positive with Flk-1 negative subset were cultured. The former subset incorporated DiI-acLDL and were integrated with HUVECs. Furthermore, they demonstrated significantly higher levels of murine vascular endothelial growth factor and interleukin-8 in culture supernatant on time course by enzyme-linked immunosorbent assay. These findings constitute direct evidence that breast cancer induces postnatal vasculogenesis in vivo.

Histological, Immunohistological, and Ultrastructural Description of Vasculogenic Mimicry in Canine Mammary Cancer

“…16,26,27,38,66,72,81 VM has been also described in experimental and spontaneous malignant breast cancer. 4,36,58,[60][61][62][63] To our knowledge, there are no previous studies of VM in spontaneous animal tumors, including canine mammary tumors and IMC.…”

Sex-steroid regulation of vascular endothelial growth factor in breast cancer

“…These cells originate in the bone marrow, can be detected in the peripheral circulation and are incorporated into sites of ongoing angiogenesis where they differentiate into mature endothelial cells (Asahara et al 1997, Lyden et al 2001. VEGF has a potential role in such recruitment and there is evidence for EPC recruitment in breast cancer cells (Asahara et al 1999, Shirakawa et al 2002a,b, Spring et al 2005. It has been reported that EPCs decline after treatment with antiangiogenic therapy (Capillo et al 2003) thus making these cells targets for such therapy (Rafii et al 2002).…”

Inhibition of Invasion and Capillary-like Tube Formation by Retrohydroxamate-based MMP Inhibitors

“…Human umbilical vascular endothelial cells (HUVECs) grown on Matrigel form a capillary-like tube network in an MMP-dependent manner. [30][31][32] Thus, the effect of 2d and 2g on the tube formation of HUVECs was analyzed. Tube formation of VEGF (10 ng/mL)-treated HUVECs was dose-dependently inhibited by 2d and 2g similar to the inhibition by BB-94 (Fig.…”