Cell-ECM Interactions in Tumor Invasion
The cancer cells obtain their invasion potential not only by genetic mutations, but also by changing their cellular biophysical and biomechanical features and adapting to the surrounding microenvironments. The extracellular matrix, as a crucial component
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Cell-ECM Interactions in Tumor Invasion Xiuxiu He, Byoungkoo Lee, and Yi Jiang
Abstract
The cancer cells obtain their invasion potential not only by genetic mutations, but also by changing their cellular biophysical and biomechanical features and adapting to the surrounding microenvironments. The extracellular matrix, as a crucial component of the tumor microenvironment, provides the mechanical support for the tissue, mediates the cell-microenvironment interactions, and plays a key role in cancer cell invasion. The biomechanics of the extracellular matrix, particularly collagen, have been extensively studied in the biomechanics community. Cell migration has also enjoyed much attention from both the experimental and modeling efforts. However, the detailed mechanistic understanding of tumor cell-ECM interactions, especially during cancer invasion, has been unclear. This chapter reviews the recent advances in the studies of ECM biomechanics, cell migration, and cell-ECM interactions in the context of cancer invasion. Keywords
Extracellular matrix • Cell-ECM interactions • Cell migration • Mathematical models • Collagen • Mechanotransduction • Cancer invasion
4.1
Introduction
The tumor microenvironment is created by proliferating tumor cells and dominated by tumor-induced interactions [112]. It has been X. He • B. Lee • Y. Jiang () Department of Mathematics and Statistics, Georgia State University, Atlanta, GA 30303, USA e-mail: [email protected]; [email protected]; [email protected]
well accepted that the tumor microenvironment plays a significant role in disease progression, but the precise function of each constituent remains unclear. The tissue microenvironment of a developing tumor can be broken down into three categories: the biological, the chemical, and the biophysical/biomechanical. The biological environment is comprised of the cellular constituents that surround the malignant cancer cells. A variety of infiltrating immune cells [112], cancer-associated fibroblasts [100], and
© Springer International Publishing Switzerland 2016 K.A. Rejniak (ed.), Systems Biology of Tumor Microenvironment, Advances in Experimental Medicine and Biology 936, DOI 10.1007/978-3-319-42023-3_4
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angiogenic endothelial cells [110] perform critical functions in sustaining cell proliferation, evading growth suppressors, promoting survival, activating invasion and metastasis, as well as reprogramming energy metabolism. The chemical environment refers to the abnormal distribution of oxygen, nutrients, wastes, and cytokines, as well as many growth factors and inhibitors. For example, excess growth of the tumor cells leads to a hypoxic environment [55], elevated oxidative stress [22], and consequently, the accumulation of lactic acid due to anaerobic metabolism [44] and up-regulation growth factor production (e.g., VEGF). The biophysical and biomechanical aspect of the tumor is both the physical and geometrical constraints from the tissue structure, and the mechanical interactions between the tumor and surrounding environm
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