1. ¹Department of Neurological Surgery, Spine Center, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
2. ²Department of Orthopaedics, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
3. ³Endocrinology, Department of Internal Medicine III, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
4. ⁴Oncology and Haematology, Department of Internal Medicine II, University Medical Center Hamburg-Eppendorf, Hamburg, Germany

Correspondence: Dr N Hansen-Algenstaedt, Spine Center and Department of Orthopedics, University Medical Center Hamburg-Eppendorf, Martinistrasse 52, Hamburg 20246, Germany. E-mail: n.hansen@uke.uni-hamburg.de

Received 4 July 2007; Revised 6 August 2007; Accepted 13 August 2007; Published online 27 September 2007.

Abstract

Functional and morphological properties of tumor microcirculation play a pivotal role in tumor progression, metastasis and inefficiency of tumor therapies. Despite enormous insights into tumor angiogenesis in solid tumors, little is known about the time-course-dependent properties of tumor vascularization in hematologic malignancies. The aim of this study was to establish a model of myeloid leukemia, which allows long-term monitoring of tumor progression and associated microcirculation. Red fluorescent protein-transduced human leukemic cell lines (M-07e) were implanted into cranial windows of severe combined immunodeficient mice. Intravital microscopy was performed over 55 days to measure functional (microvascular permeability, tissue perfusion rate and leukocyte–endothelium interactions) and morphological vascular parameters (vessel density, distribution and diameter). Tumor progression was associated with elevated microvascular permeability and an initial angiogenic wave followed by decreased vessel density combined with reduced tissue perfusion due to loss in small vessels and development of heterogenous tumor vascularization. Following altered geometric resistance of microcirculation, leukocyte–endothelium interactions were more frequent without increased leukocyte extravasation. It was concluded that time-dependent alterations of leukemic tumor vascularization exhibit strong similarities to those found in solid tumors. The potential contribution to the development of barriers to drug delivery in leukemic tumors is discussed.