Abstract
Blood vessel micro-angioarchitecture plays a pivotal role in tumor progression, metastatic dissemination and response to therapy. Thus, methods able to quantify microvascular trees and their anomalies may allow a better comprehension of the neovascularization process and evaluation of vascular-targeted therapies in cancer. To this aim, the development of a restricted set of indexes able to describe the arrangement of a microvascular tree is eagerly required. We addressed this goal through 3D analysis of the functional microvascular network in sulfo-biotin-stained human multiple myeloma KMS-11 xenografts in NOD/SCID mice. Using image analysis, we show that amounts, spatial dispersion and spatial relationships of adjacent classes of caliber-filtered microvessels provide a near-linear graphical “fingerprint” of tumor micro-angioarchitecture. Position, slope and axial projections of this graphical outcome reflect biological features and summarize the properties of tumor micro-angioarchitecture. Notably, treatment of KMS-11 xenografts with anti-angiogenic drugs affected position and slope of the specific curves without degrading their near-linear properties. The possibility offered by this procedure to describe and quantify the 3D features of the tumor micro-angioarchitecture paves the way to the analysis of the microvascular tree in human tumor specimens at different stages of tumor progression and after pharmacologic interventions, with possible diagnostic and prognostic implications.
Highlights
The micro-angioarchitecture of a tissue is a major parameter underlying its functional properties in terms of oxygen supply, nutrient and drug delivery
In our previous work[18], we quantified the sulfo-biotin-stained vasculature of human multiple myeloma KMS-11 xenografts by a 3D approach based on amounts and spatial dispersion of caliber-classified microvessels taking into consideration the fluorescent signal upon subdivision of vessels according to their approximated caliber
In order to understand whether the micro-angioarchitectural changes observed with sunitinib and sorafenib were related to their anti-angiogenic mechanism of action, we extended our analysis to KMS-11 tumors treated with the vascular disrupting agent CA-4P22
Summary
The micro-angioarchitecture of a tissue is a major parameter underlying its functional properties in terms of oxygen supply, nutrient and drug delivery. A better resolution can be achieved by acoustic angiography that can be used to define the spatial coordinates occupied by individual vessels, allowing the quantification of vascular tortuosity metrics for early tumor detection and evaluation of the changes in the vascular microenvironment during tumor progression[13,14,15]. In this case, the resolution of contrast-enhanced images of superficial microvasculature (~150 μm) does not allow the analysis of capillaries or neoangiogenic sprouts
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