Charting the unexplored extracellular matrix in cancer

Abstract

The extracellular matrix (ECM) is present in all solid tissues and considered a master regulator of cell behaviour and phenotype. The importance of maintaining the correct biochemical and biophysical properties of the ECM, and the subsequent regulation of cell and tissue homeostasis, is illustrated by the simple fact that the ECM is highly dysregulated in many different types of disease, especially cancer. The loss of tissue ECM homeostasis and integrity is seen as one of the hallmarks of cancer and typically defines transitional events in progression and metastasis. The vast majority of cancer studies place an emphasis on exploring the behaviour and intrinsic signalling pathways of tumour cells. Their goal was to identify ways to target intracellular pathways regulating cancer. Cancer progression and metastasis are powerfully influenced by the ECM and thus present a vast, unexplored repository of anticancer targets that we are only just beginning to tap into. Deconstructing the complexity of the tumour ECM landscape and identifying the interactions between the many cell types, soluble factors and extracellular-matrix proteins have proved challenging. Here, we discuss some of the emerging tools and platforms being used to catalogue and chart the ECM in cancer.

Keywords: cancer; extracellular matrix; imaging; metastasis; proteomics; remodelling.

Figure 1

Overview of the basic building blocks of the extracellular matrix that come together to form the highly ordered supramolecular structures that contribute to the various interstitial matrix, microfibrils and the basal laminae within tissues. [Colour figure can be viewed at http://wileyonlinelibrary.com]

Figure 2

Simplified representation of the extracellular matrix. Made up of many molecules that come together to form the highly ordered supramolecular structures, and the extracellular matrix, through its various cell surface receptors, modulates a number of downstream intracellular signalling pathways to determine cell phenotype and behaviour. [Colour figure can be viewed at http://wileyonlinelibrary.com]

Figure 3

Multiplexing new platforms to study the extracellular matrix in health and disease. Approaches such as tissue decellularization significantly boost our ability to, and resolution at which we can study the extracellular matrix in downstream applications such as; (a) confocal and light sheet microscopy; (b) proteomic cataloguing using liquid chromatography‐mass spectrometry and computational analysis; (c) MALDI‐Mass Spec Imaging (MALDI‐MSI) and spatial mapping of ECM components. [Colour figure can be viewed at http://wileyonlinelibrary.com]