Abstract
Simple SummaryExtracellular matrix is a three-dimensional network of macromolecules that provide structural and biochemical support to surrounding cells. Extracellular matrix plays a critical role in the development and progression of cancer. The extracellular matrix of the tumor is very different from the matrix of the normal tissue. Mainly fibroblasts produce and regulate matrix remodeling, but in cancer, the tumor matrix also originates from cancer cells. We describe the mechanisms of how the protein composition and structure of the extracellular matrix changes during cancer progression and how abnormal matrix deregulates the behavior of stromal cells and influences cancer progression.The extracellular matrix (ECM) is highly dynamic as it is constantly deposited, remodeled and degraded to maintain tissue homeostasis. ECM is a major structural component of the tumor microenvironment, and cancer development and progression require its extensive reorganization. Cancerized ECM is biochemically different in its composition and is stiffer compared to normal ECM. The abnormal ECM affects cancer progression by directly promoting cell proliferation, survival, migration and differentiation. The restructured extracellular matrix and its degradation fragments (matrikines) also modulate the signaling cascades mediated by the interaction with cell-surface receptors, deregulate the stromal cell behavior and lead to emergence of an oncogenic microenvironment. Here, we summarize the current state of understanding how the composition and structure of ECM changes during cancer progression. We also describe the functional role of key proteins, especially tenascin C and fibronectin, and signaling molecules involved in the formation of the tumor microenvironment, as well as the signaling pathways that they activate in cancer cells.
Highlights
The tumor microenvironment is a highly heterogeneous environment around a tumor, that includes cellular components and a non-cellular component termed the extracellular matrix (ECM).During cancer progression, carcinoma cells recruit host stromal cells, which change their properties and metabolism, and together they create a unique microenvironment to cooperatively remodel the surrounding matrix and promote tumor invasion [1]
Degradation of ECM is not a passive event as it is accompanied by the release of matrixbound growth factors as well as matrikines that interact with multiple surface receptors and trigger signal transduction, regulating tumor growth and cell migration [6,7]
This review aims to present the functional role of ECM components in tumor development, with particular emphasis on the involvement of fibronectin and tenascin in this process
Summary
The tumor microenvironment is a highly heterogeneous environment around a tumor, that includes cellular components (fibroblasts, endothelial cells, adipocytes, immune and inflammatory cells) and a non-cellular component termed the extracellular matrix (ECM). Carcinoma cells recruit host stromal cells, which change their properties and metabolism, and together they create a unique microenvironment to cooperatively remodel the surrounding matrix and promote tumor invasion [1]. Tumor cells secrete extracellular vesicles with nucleic acids, lipids and proteins, which can participate in tumor progression and behavior, including tumor environment remodeling, fibroblast activation, angiogenesis, immunomodulation or the establishment of pre-metastatic niches [4,5]. We describe the relationships between cancer cells and cancer-associated fibroblasts, and the mechanisms by which cancerized ECM can modulate tumor progression and aggressiveness
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