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.

Marine Collagen Substrates for 2D and 3D Ovarian Cancer Cell Systems

“…The interplay between cancer cells, tissue resident cells and the surrounding extracellular matrix (ECM) strongly affect cancer tumorigenesis and progression. Specifically, the loss of integrity and homeostasis in tissue ECM is a crucial cancer hallmark, with a defined "matrisome" signature for both normal and diseased tissue demonstrating how microenvironment components are deregulated during a pathologic event (Naba et al, 2012(Naba et al, , 2014a(Naba et al, ,b, 2017Filipe et al, 2018;Pearce et al, 2018). 3D models aim to replicate tissue mechanical properties, providing optimal bioactive structures for cell attachment and proliferation to preserve native cellular phenotypes.…”

Recent advances in understanding the complexities of metastasis

“…Because the majority of structural ECM proteins exhibit a remarkable longevity in vivo , often measured in weeks and months and even years 8 , as opposed to hours for intracellular proteins, we argue that the tumour-specific blend of ECM molecules records a history of tumour evolution 132 . As such, it has the potential to allow us to better understand how a specific tumour has emerged.…”

The Mini‐Organo: A rapid high‐throughput 3D coculture organotypic assay for oncology screening and drug development

“…Because collagen I represents the major interstitial ECM component of most tissues, including many solid tumours, the Mini‐Organo offers a physiologically relevant and powerful approach to assessing potential stromal cell targeting in the cancer context. Targeting ECM remodelling as an approach to treat solid tumours is an exciting emerging concept that is showing promise in several settings …”

“…Mammalian tissues are highly complex microenvironments where a close interplay exists between the cellular and acellular compartments. [1][2][3][4] This complex and reciprocal interaction is technically challenging to reproduce in vitro as both healthy and diseased tissues co-evolve over time. Furthermore, in vivo study of these complex tissue environments is time-consuming and labour intensive, and experimental manipulation is typically limited.…”

“…[19][20][21] Extracellular matrix deposition, contraction, and remodelling are common to diseases such as tissue fibrosis, diabetes, and tissue aging and importantly are salient features of almost all solid tumours. 3,22 Prior to and during malignant transformation and tumour expansion, the host stroma typically initiates a desmoplastic stromal response. 1,[23][24][25][26] This response leads to a significant deposition and remodelling of the ECM within and surrounding the tumour.…”