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Updated: Jun 4, 2026
Kinetic Analysis of Vasculogenesis Quantifies Dynamics of Vasculogenesis and Angiogenesis In Vitro
Published on: January 31, 2018
A multiscale hybrid approach for vasculogenesis and related potential blocking therapies
Marco Scianna1, Luca Munaron, Luigi Preziosi
1Department Of Mathematics, Politecnico Di Torino, Corso Duca degli Abruzzi 24, 10129 Torino, Italy.
Abstract:
Solid tumors must recruit and form new blood vessels for maintenance, growth and detachments of metastases. Discovering drugs that block malignant angiogenesis is thus an important approach in cancer treatment and has given rise to multiple in vitro and in silico models. The present hybrid individual cell-based model incorporates some underlying biochemical events relating more closely the classical Cellular Potts Model (CPM) parameters to subcellular mechanisms and to the activation of specific signaling pathways. The model spans the three fundamental biological levels: at the extracellular level a continuous model describes secretion, diffusion, uptake and decay of the autocrine VEGF; at the cellular level, an extended lattice CPM, based on a system energy reduction, reproduces cell dynamics such as migration, adhesion and chemotaxis; at the subcellular level, a set of reaction-diffusion equations describes a simplified VEGF-induced calcium-dependent intracellular pathway. The results agree with the known interplay between calcium signals and VEGF dynamics and with their role in malignant vasculogenesis. Moreover, the analysis of the link between the microscopic subcellular dynamics and the macroscopic cell behaviors confirms the efficiency of some pharmacological interventions that are currently in use and, more interestingly, proposes some new therapeutic approaches, that are counter-intuitive but potentially effective.
Insights
This study presents a hybrid model of tumor angiogenesis, linking subcellular signaling to cell behavior. The model validates existing cancer therapies and suggests novel, counter-intuitive treatment strategies.
Area of Science:
- Computational Biology
- Cancer Research
- Biophysics
Background:
- Solid tumors require angiogenesis for growth and metastasis.
- Targeting malignant angiogenesis is a key cancer treatment strategy.
- Existing in vitro and in silico models have limitations in capturing complex biological interactions.
Purpose of the Study:
- To develop a hybrid individual cell-based model integrating biochemical events with cellular dynamics.
- To link subcellular mechanisms, like VEGF signaling and calcium pathways, to macroscopic cell behaviors.
- To evaluate current and propose novel therapeutic interventions for malignant angiogenesis.
Main Methods:
- A hybrid model combining continuous extracellular modeling (VEGF), extended Cellular Potts Model (CPM) for cell dynamics, and reaction-diffusion equations for intracellular pathways (calcium signaling).
- Modeling spans extracellular, cellular, and subcellular biological levels.
- Analysis focused on the interplay between VEGF, calcium dynamics, and cell behavior.
Main Results:
- The model accurately reflects the known interactions between calcium signals and VEGF dynamics in malignant vasculogenesis.
- It confirms the efficacy of established pharmacological interventions.
- It identifies potentially effective, novel therapeutic approaches.
Conclusions:
- The hybrid model effectively bridges subcellular biochemical processes with emergent cellular behaviors in angiogenesis.
- The findings support the use of integrated modeling for understanding cancer biology and drug development.
- The study proposes new, potentially counter-intuitive therapeutic strategies targeting tumor angiogenesis.
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