What types of cancer are associated with chronic inflammation?
Oxidative Stress, Inflammatory Processes, and Cancer: How Are They Linked?
Chronic inflammation has been linked to various steps in cancer development, including cellular transformation (degeneration), promotion, survival, division, invasion, angiogenesis, and metastasis. Cancer is a multi-step process that is defined by at least three steps: initiation, promotion and progression. Oxidative stress affects all three stages of this process. During the initiation phase, ROS can cause DNA damage. In the promotional phase, ROS can contribute to abnormal gene expression, blockage of cell-cell communication and changes in messenger substances, which can lead to an increase in cell division or a decrease in apoptosis (programmed cell death) in the degenerating cell population. Oxidative stress can also be involved in tumor progression by adding further DNA changes to the degenerate cell population. In recent years, there is ample evidence that ROS is implicated in the link between chronic inflammation and cancer. An important feature of tumor promoters is to recruit pro-inflammatory cells and stimulate them to produce ROS. In fact, in initial experiments on the role of ROS in tumor initiation, it was assumed that oxidative stress is DNA-damaging, thus increasing the mutation rate within the cells and thus promoting oncogenic transformation (degeneration). However, recent studies have shown that ROS not only cause genomic instability, but also activate cellular signaling pathways. These signaling pathways regulate, for example, cell division, the growth of blood vessels (angiogenesis) and metastasis and thus contribute to the development of cancer. One of the main characteristics of tumor cells is their increased viability compared to normal cells. This ability to survive is mediated by altered cellular signaling pathways. It is known, for example, that ROS are able to activate the signal protein actin. Active actin prevents apoptosis and increases oxygen metabolism within the cell, both of which promote cell survival. Another characteristic of tumors is their uncontrolled cell division of the tumor cells. This uncontrolled cell division in turn requires the upregulation of various cellular signal cascades. Tumor invasion and metastasis, which are important features of aggressive tumors and cancers, can also be intensified by oxygen radicals. This can be done via signal molecules and matrix metalloproteases. Matrix metalloproteases are able to cleave components of the basement membrane. This in turn leads to the tumor cells losing contact with the place of origin and thus more easily metastasizing or penetrating deeper tissue layers. Angiogenesis can also be influenced by ROS. Angiogenic growth factors (e.g. VEGF, FGF and PDGF) are released into the tumor microenvironment by tumor cells or inflammation-promoting cells in response to, among other things, ROS. The released growth factors activate endothelial cells, which create new blood vessels.
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