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Updated: Aug 7, 2025
Monitoring Functionality and Morphology of Vasculature Recruited by Factors Secreted by Fast-growing Tumor-generating Cells
Published on: November 23, 2014
Investigation of the evolution of tumor-induced microvascular network under the inhibitory effect of anti-angiogenic
Mahya Mohammadi1,2, M Soltani1,3,4,5,6, Cyrus Aghanajafi1
1Department of Mechanical Engineering, K. N. Toosi University of Technology, Tehran 19919-43344, Iran.
Abstract:
Anti-angiogenesis as a treatment strategy for normalizing the microvascular network of tumors is of great interest among researchers, especially in combination with chemotherapy or radiotherapy. According to the vital role that angiogenesis plays in tumor growth and in exposing the tumor to therapeutic agents, this work develops a mathematical framework to study the influence of angiostatin, a plasminogen fragment that shows the anti-angiogenic function, in the evolutionary behavior of tumor-induced angiogenesis. Angiostatin-induced microvascular network reformation is investigated in a two-dimensional space by considering two parent vessels around a circular tumor by a modified discrete angiogenesis model in different tumor sizes. The effects of imposing modifications on the existing model, i.e., the matrix-degrading enzyme effect, proliferation and death of endothelial cells, matrix density function, and a more realistic chemotactic function, are investigated in this study. Results show a decrease in microvascular density in response to the angiostatin. A functional relationship exists between angiostatin's ability to normalize the capillary network and tumor size or progression stage, such that capillary density decreases by 55%, 41%, 24%, and 13% in tumors with a non-dimensional radius of 0.4, 0.3, 0.2, and 0.1, respectively, after angiostatin administration.
Insights
This study models how angiostatin affects tumor blood vessel growth. Angiostatin significantly reduces microvascular density, with greater effects in larger tumors, offering a potential strategy for cancer treatment.
Area of Science:
- Oncology
- Mathematical Biology
- Biophysics
Background:
- Anti-angiogenesis is a promising cancer treatment strategy, particularly when combined with chemotherapy or radiotherapy.
- Tumor angiogenesis is crucial for tumor growth and drug delivery.
- Angiostatin, a plasminogen fragment, exhibits anti-angiogenic properties.
Purpose of the Study:
- To develop a mathematical framework for studying the influence of angiostatin on tumor-induced angiogenesis.
- To investigate angiostatin-induced microvascular network reformation in a 2D space using a modified discrete angiogenesis model.
- To analyze the impact of model modifications, including enzyme effects, endothelial cell dynamics, and chemotaxis, on angiogenesis.
Main Methods:
- A modified discrete angiogenesis model was employed in a two-dimensional space.
- The model simulated a circular tumor with two parent vessels.
- Key factors such as matrix-degrading enzyme activity, endothelial cell proliferation and death, matrix density, and chemotaxis were incorporated and modified.
Main Results:
- Angiostatin administration led to a notable decrease in microvascular density within tumors.
- A direct relationship was observed between angiostatin's efficacy in normalizing the capillary network and tumor size.
- Capillary density reductions ranged from 13% in smaller tumors (radius 0.1) to 55% in larger tumors (radius 0.4).
Conclusions:
- The mathematical model successfully demonstrates angiostatin's anti-angiogenic effect.
- Angiostatin's effectiveness in normalizing tumor vasculature is dependent on tumor size and progression stage.
- These findings support the potential of angiostatin as a therapeutic agent for modulating tumor angiogenesis.
Related Concept Videos
01:24Regulation of Angiogenesis and Blood Supply
01:10Mechanism of Angiogenesis
02:17The Tumor Microenvironment