The development of tumour vascular networks

Anahita Fouladzadeh,Claudine S Bonder,Johan W Verjans,Michaelia P Cockshell,Andrew Allison,Kay Khine Myo Min,Mohsen Dorraki,Emma J Thompson,Derek Abbott

doi:10.1038/s42003-021-02632-x

Abstract

The growth of solid tumours relies on an ever-increasing supply of oxygen and nutrients that are delivered via vascular networks. Tumour vasculature includes endothelial cell lined angiogenesis and the less common cancer cell lined vasculogenic mimicry (VM). To study and compare the development of vascular networks formed during angiogenesis and VM (represented here by breast cancer and pancreatic cancer cell lines) a number of in vitro assays were utilised. From live cell imaging, we performed a large-scale automated extraction of network parameters and identified properties not previously reported. We show that for both angiogenesis and VM, the characteristic network path length reduces over time; however, only endothelial cells increase network clustering coefficients thus maintaining small-world network properties as they develop. When compared to angiogenesis, the VM network efficiency is improved by decreasing the number of edges and vertices, and also by increasing edge length. Furthermore, our results demonstrate that angiogenic and VM networks appear to display similar properties to road traffic networks and are also subject to the well-known Braess paradox. This quantitative measurement framework opens up new avenues to potentially evaluate the impact of anti-cancer drugs and anti-vascular therapies.

Highlights

The growth of solid tumours relies on an ever-increasing supply of oxygen and nutrients that are delivered via vascular networks
How do gene networks drive the biology of breast cancer1? Can network analysis assist C-reactive protein forecasting2,3? Which proteins have the highest number of interactions with other proteins? How long does it take for a signal from the brain to reach the limbs? What is the shortest path of reactions that transforms one metabolite into another? What is the role of cell signalling networks in the relationship between molecular species4? How does adopting a particular strategy lead to survival in a species under a competition5? How does a growing tumour increase its oxygen and nutrient supply? Such questions may potentially be addressed if we investigate the topology and morphology of the networks, i.e., the way contributing factors connect and interact
To investigate the dynamics of this process, we designed an in vitro study to display the networks formed by cells; we investigated the cell growth for angiogenesis using endothelial colony-forming cells (ECFCs) and vasculogenic mimicry (VM)

Summary

Introduction

The growth of solid tumours relies on an ever-increasing supply of oxygen and nutrients that are delivered via vascular networks. To study and compare the development of vascular networks formed during angiogenesis and VM (represented here by breast cancer and pancreatic cancer cell lines) a number of in vitro assays were utilised. Analysing the structure, topology and morphology of the graph representing a biological network may provide useful statistical information, which eventually assists in developing a mathematical or computational model The challenge with such an approach is that it is not immediately evident how mathematics might elucidate biology. We directly compare the development of angiogenic EC networks with cancer cell formed VM networks with a focus on a human breast cancer cell line[25] (MDA-MB231 cells and their metastatic derivative MDA-MB-231-LM2) and two human pancreatic cancer cell lines[26] (BxPC-3 and AsPC-1 cells) This comparison builds on our understanding of the vasculogenic patterns that contribute to cancer progression

Methods

Results

Conclusion