Fascin 1 is dispensable for developmental and tumour angiogenesis

Yafeng Ma,Laura M Machesky,Shigeko Yamashiro,Kairbaan M Hodivala-Dilke,Richard P Stevenson,Ang Li,Louise E Reynolds

doi:10.1242/bio.20136031

Abstract

SummaryThe actin bundling protein fascin 1 is not expressed in adult epithelial tissues, but during development it is transiently expressed in many different cell types, and later in adults it is expressed in a subset of immune cells, nervous tissues, endothelial cells, smooth muscle cells and pericytes. In contrast to the wealth of knowledge about the role of fascin 1 in cancer cell migration and invasion, little is known about the involvement of fascin 1 in angiogenesis. We speculated that as angiogenesis involves migration and invasion of tissues by endothelial cells, fascin 1 might have a role in both normal and tumour angiogenesis. Here, we provide evidence that loss of fascin 1 causes relatively minor reductions to angiogenesis during embryonic, postnatal and cancerous development by examining E12.5 hindbrains, postnatal retinas and B16F0 tumour cell allografts in fascin 1-null mice. We also find that in fascin 1 null tissues, endothelial cells display reduced filopodia formation during sprouting. We thus propose that fascin 1 expression promotes angiogenesis via filopodia formation, but is largely dispensable for both normal and tumour angiogenesis.

Highlights

Angiogenesis, the formation of new capillaries from existing vessels, is a fundamental process in development and tumour growth
Summary The actin bundling protein fascin 1 is not expressed in adult epithelial tissues, but during development it is transiently expressed in many different cell types, and later in adults it is expressed in a subset of immune cells, nervous tissues, endothelial cells, smooth muscle cells and pericytes
In contrast to the wealth of knowledge about the role of fascin 1 in cancer cell migration and invasion, little is known about the involvement of fascin 1 in angiogenesis

Summary

Introduction

Angiogenesis, the formation of new capillaries from existing vessels, is a fundamental process in development and tumour growth. It involves multiple cell types in sequential controlled steps. Various growth factors such as vascular endothelial growth factors (VEGFs) (Ruhrberg et al, 2002; Gerhardt et al, 2003; Nakayama et al, 2013), Notch pathway components (Roca and Adams, 2007) and cell adhesion molecules (Reynolds et al, 2002; Silva et al, 2008) including integrins have been reported to play crucial roles in angiogenesis and vasculogenesis. Besides its upregulated expression in some motile progenitor cells during embryogenesis (Hayashi et al, 2008; Chae et al, 2009; Zanet et al, 2009; Ma et al, 2013) and many epithelial cancers (Machesky and Li, 2010), fascin 1 is moderately or highly expressed in endothelial cells (ECs) and mural cells in normal adult tissue and primary cell culture (Jawhari et al, 2003; Zhang et al, 2008; Hoelzle and Svitkina, 2012)

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