Decellularized Colorectal Cancer Matrices as Bioactive Scaffolds for Studying Tumor-Stroma Interactions

Abstract

More than a physical structure providing support to tissues, the extracellular matrix (ECM) is a complex and dynamic network of macromolecules that modulates the behavior of both cancer cells and associated stromal cells of the tumor microenvironment (TME). Over the last few years, several efforts have been made to develop new models that accurately mimic the interconnections within the TME and specifically the biomechanical and biomolecular complexity of the tumor ECM. Particularly in colorectal cancer, the ECM is highly remodeled and disorganized and constitutes a key component that affects cancer hallmarks, such as cell differentiation, proliferation, angiogenesis, invasion and metastasis. Therefore, several scaffolds produced from natural and/or synthetic polymers and ceramics have been used in 3D biomimetic strategies for colorectal cancer research. Nevertheless, decellularized ECM from colorectal tumors is a unique model that offers the maintenance of native ECM architecture and molecular composition. This review will focus on innovative and advanced 3D-based models of decellularized ECM as high-throughput strategies in colorectal cancer research that potentially fill some of the gaps between in vitro 2D and in vivo models. Our aim is to highlight the need for strategies that accurately mimic the TME for precision medicine and for studying the pathophysiology of the disease.

Keywords: colorectal cancer; extracellular matrix; patient-derived scaffolds.

Figure 1

The extracellular matrix contributes to the hallmarks of cancer. The bioactive role of the extracellular matrix has been described to be involved in eight of the ten well-known hallmarks of cancer reported by Hanahan and Weinberg in 2011 [8], namely in resisting cell death, sustaining proliferative signaling, deregulating cellular energetics, avoiding immune destruction, tumor-promoting inflammation, evading factors, inducing angiogenesis, and activating invasion and metastasis. The influence of the extracellular matrix in the other two hallmarks (genome instability and mutation and enabling replicative immortality) is not yet fully characterized in CRC. Created with BioRender.com (accessed on 10 November 2021).

Figure 2

Patient-derived decellularized scaffold as a suitable tool for studying tumor–stroma interactions. The decellularization process of patient-derived tissue allows the efficient removal of the cellular component of the ECM, maintaining the 3D structure, as well as the biochemical categories (core matrisome and matrisome-associated proteins), according to Naba et al. [150], and biomechanical properties (stiffness). Created with BioRender.com (accessed on 10 November 2021).