Reactive oxygen species: a volatile driver of field cancerization and metastasis

Abstract

Field cancerization and metastasis are the leading causes for cancer recurrence and mortality in cancer patients. The formation of primary, secondary tumors or metastasis is greatly influenced by multifaceted tumor-stroma interactions, in which stromal components of the tumor microenvironment (TME) can affect the behavior of the cancer cells. Many studies have identified cytokines and growth factors as cell signaling molecules that aid cell to cell communication. However, the functional contribution of reactive oxygen species (ROS), a family of volatile chemicals, as communication molecules are less understood. Cancer cells and various tumor-associated stromal cells produce and secrete a copious amount of ROS into the TME. Intracellular ROS modulate cell signaling cascades that aid in the acquisition of several hallmarks of cancers. Extracellular ROS help to propagate, amplify, and effectively create a mutagenic and oncogenic field which facilitate the formation of multifoci tumors and act as a springboard for metastatic tumor cells. In this review, we summarize our current knowledge of ROS as atypical paracrine signaling molecules for field cancerization and metastasis. Field cancerization and metastasis are often discussed separately; we offer a model that placed these events with ROS as the focal instigating agent in a broader “seed-soil” hypothesis.

Iron and copper complexes with antioxidant activity as inhibitors of the metastatic potential of glioma cells

“…In addition to having an effect on intracellular ROS levels, we cannot rule out the possibility that the complexes used are also altering extracellular ROS levels. These species have been hypothesized to be extremely relevant players in the tumor microenvironment and different aspects of cancer progression, including the development of metastasis, 41 and, as such, this possibility is worthy of further investigation in the future.…”

Radiation Induced Metabolic Alterations Associate with Tumor Aggressiveness and Poor Outcome in Glioblastoma

“…Radiation treatment leads to production of ROS. Tumors adapt to oxidative stress through several mechanisms, including metabolic shifts and elevated antioxidant peptide production and intratumoral hypoxia generation (48)(49)(50). Metabolomics has emerged as the state-of-the-art approach to identify cancer cell state and biomarkers.…”

“…ROS production is associated with DNA damage and cell death. However, chronically high levels of ROS in the tumor microenvironment can be pro-tumorigenic (50,60). Similarly, while ATP and GTP are essential components of cellular homeostasis, a rise in intracellular nucleotides (ATP and GTP) can cause their export out of the cell through extracellular vesicles, thus elevating extracellular levels of nucleoside and nucleotides (eATP, eGTP, adenosine and guanine) (61,62).…”

Activation of reactive oxygen species-mediated mitogen-activated protein kinases pathway regulates both extrinsic and intrinsic apoptosis induced by arctigenin in Hep G2

“…Numerous studies have reported that MAPKs are involved in the signal transduction processes in tumour cells exposed to anticancer agents . Diverse reactive oxygen species (ROS) produced during cellular metabolism play important roles in cell death, hormone secretion, ion transport, ATP production, immunomodulation, etc . It has been reported that cell aerobic respiration coupled to the generation of ATP leads to the formation of superoxide anion radicals (·O 2 − ) through an enzymatic reaction converting·O 2 − to hydrogen peroxide (H 2 O 2 ) or highly reactive hydroxyl radicals (·OH) .…”

“…[12,13] Diverse reactive oxygen species (ROS) produced during cellular metabolism play important roles in cell death, hormone secretion, ion transport, ATP production, immunomodulation, etc. [14] It has been reported that cell aerobic respiration coupled to the generation of ATP leads to the formation of superoxide anion radicals (ÁO 2 À ) through an enzymatic reaction convert-ingÁO 2 À to hydrogen peroxide (H 2 O 2 ) or highly reactive hydroxyl radicals (ÁOH). [15] Oxidative stress occurs when ROS are excessively produced or antioxidants are depleted.…”