The effect of Bone Morphogenetic Proteins and Lysyl Oxidases in the tumor vasculature

Abstract

Cancer progression is a complex process involving both tumor cells and a variety of non-malignant somatic cells. Recent studies suggest that the extracellular matrix is extremely important in the context of cancer as it interacts with cells to control their behaviour. ECM molecules are highly organized to meet the needs of their cellular environment, and this organization determines the bioactivity of the ECM. It has therefore been proposed that alterations in the microenvironment of cancer cells, i.e. ECM build-up and remodelling, can lead to metastasis. Lysyl oxidases are a family of copper-dependent enzymes which play a role in ECM remodelling by cross-linking the structural proteins collagen and elastin, thus maintaining the strength and stiffness of the ECM. Lysyl oxidases have been reported to augment migration, progression, invasion and metastasic spreading in various cancers by means of their ability to regulate the stiffness of the ECM.Preliminary data of the research group suggests that BMP9 promotes endothelial expansion of human embryonic stem cells and sprouting via EGFL7. Data has shown that EGFL7 is expressed and secreted by endothelial cells and it has been proposed to modulate the stiffness of the ECM to promote cell migration and invasion. The aim of this project was to examine whether lysyl oxidases are secreted by endothelial cells via BMP9-induced EGFL7 and if it has any effect on breast cancer cell migration. Unravelling the interplay between BMP signalling components, lysyl oxidases and the ECM components will enable us to map these patwhays and exploit them to develope targeted molecular therapies for breast cancer patients to reduce metastatic spreading and hopfully regression of the cancer.