The Biomechanical Properties of 3d Extracellular Matrices and Embedded Cells Regulate the Invasiveness of Cancer Cells

Abstract

The malignancy of tumors depends on the biomechanical properties of cancer cells and their microenvironment, which enable cancer cells to migrate through the connective tissue, transmigrate through basement membranes and endothelial monolayers and form metastases in targeted organs. The current focus of cancer research is still based on biological capabilities such as molecular genetics and gene signaling, but these approaches ignore the mechanical nature of the invasion process of cancer cells. This review will focus on how structural, biochemical and mechanical properties of extracellular matrices (ECMs), and adjacent cells regulate the invasiveness of cancer cells. In addition, it presents how cancer cells create their own microenvironment by restructuring of the ECM and by interaction with stromal cells, which then further contribute to the progression of cancer disease. Finally, this review will point out that mechanical properties are a critical determinant for the efficiency of cancer cell invasion and the progression of cancer which might affect the future development of new cancer treatments.

Tumor-Associated Macrophages as Incessant Builders and Destroyers of the Cancer Stroma

“…In the last decades the concept that the ECM is simply a supporting structure for the preservation of tissue architecture has dramatically changed [160]. Indeed, ECM components provide signals affecting cell adhesion, migration, proliferation and differentiation.…”

Effect of Nuclear Stiffness on Cell Mechanics and Migration of Human Breast Cancer Cells

“…Cell migration and invasion are inherently coupled to cell mechanics and matrix environmental mechanics (Mierke et al, 2008(Mierke et al, , 2011a(Mierke et al, ,b, 2018Baker and Chen, 2012;Fruleux and Hawkins, 2016;Dietrich et al, 2018;Mierke, 2019a), or in other words their elastic properties, such as stiffness. Cell mechanics are intertwined with matrix mechanics, since the environmental mechanics can alter cell mechanics and in turn cells can remodel the surrounding matrix environment by exerting forces on it (Wolf et al, 2009(Wolf et al, , 2013Mierke, 2011;Mierke et al, 2011bMierke et al, , 2017Fischer et al, 2017;Kunschmann et al, 2019). Another way for matrix remodeling is through matrix-metalloproteinases that are secreted by cells to degrade steric hindrances for cell migration (Mierke et al, 2011a;Yu et al, 2012;Wolf et al, 2013;Davidson et al, 2014;Harada et al, 2014;Denais et al, 2016;Das et al, 2017Das et al, , 2019.…”

In Vitro Modeling of Mechanics in Cancer Metastasis

“… 33 , 34 Mechanical cues can originate from direct application of different types of forces on the cell, such as tensile, compressive, pressure, and shear forces, or structural and mechanical properties of the cellular environment such as stiffness and the microstructural architecture of the ECM. 35 − 37 Signals detected via mechanosensory systems activate intracellular signaling cascades which result in transduction of mechanical cues into intracellular biochemical events that in turn regulate cellular behavior and function such as the cell cycle, morphogenesis, and migration. 38 In the context of cancer invasion, unique biomechanical signals generated during tumor initiation and progression perturb the normal behavior of cells within and adjacent to the tumor, and the initiation of complex biomechanical signaling and mechanotransduction processes can expedite the transformation of primary cancer cells to a malignant phenotype.…”