Dynamics of microvascular remodelling during tumor growth in bone.

Microcirculatory properties of tumors have been shown to play a pivotal role in tumor progression and inefficacy of therapies. Although the influence of the microenvironment on angiogenesis has been intensively investigated in soft tissue tumors, little is known about the microvascular properties in bone metastasis. To determine the impact of the bone microenvironment on tumor growth and microcirculation we performed intravital microscopy using the "femur window" after implantation of red-fluorescent-protein-transduced breast cancer cells into the femura of severe-combined-immunodeficient mice. Tumor size, functional vascular density, vessel diameter, and vessel distribution were quantified over 14 days. Tumor growth and microcirculation could be quantified at a high spatial resolution. Tumor progression was associated with a rapid remodeling process of the microcirculation within the tumor and the surrounding tissue. Although the total functional vascular density remained unaltered, we found a significant loss in small vessels and a concomitant increase in vascular diameter. The presented study demonstrates for the first time dynamics of morphological microcirculatory alterations of tumor growth in bone. The observed changes in tumor vascularization exhibit strong similarities to soft tissue tumors; however, the dynamics of vascular alterations are more rapid in the bone microenvironment.