Sublethal oxidative stress inhibits tumor cell adhesion and enhances experimental metastasis of murine mammary carcinoma

Abstract

We have postulated that murine mammary tumor progression is fueled, in part, by tumor-associated macrophages that deliver sub-lethal oxidative stress to tumor cells. In the present study, we determined whether oxidative stress would affect murine mammary tumor cell attachment to laminin and fibronectin, critical functions in the metastatic process. Sublethal oxidative stress generated by exposure of cells to hydrogen peroxide (H2O2, 1-1000 microM/L) inhibited tumor cell attachment to immobilized laminin or fibronectin. This oxidant effect was blocked in the presence of catalase which removes H2O2. The inhibitory effect on attachment was rapid, with significant inhibition occurring at 5 min; total inhibition was achieved at 60 min with 1 mM H2O2. The oxidative stress effect was partially reversible at 20 h post-treatment and occurred at concentrations of H2O2 that do not adversely affect cell viability or growth. Pretreatment of tumor cells with H2O2 or hypoxanthanine and xanthine oxidase (to generate superoxide radical and H2O2) prior to intravenous injection, enhanced experimental lung tumor colony formation. The enhancement of experimental metastatic potential with enzyme-generated oxidative stress was completely reversed by catalase; the H2O2-mediated enhancement was only partially reversed with catalase. Thus, treatments that inhibit tumor cell attachment to extracellular matrix proteins in vitro enhance experimental metastasis in vivo.

Oxidative Stress Is Inherent in Prostate Cancer Cells and Is Required for Aggressive Phenotype

“…In addition to regulating tumor growth and survival, ROS also participate in those mechanisms that are associated with the tumor metastasis, such as migration and invasion (45). Oxidative stress may augment tumor invasion and metastasis by increasing the rate of the cell migration (46). We made a novel observation that the cell lines with higher ROS are more migratory and invasive than the cell lines with low ROS.…”

A Novel RNA-Binding Protein, Ossa/C9orf10, Regulates Activity of Src Kinases To Protect Cells from Oxidative Stress-Induced Apoptosis

“…Such reperfusion causes the generation of ROS, which may therefore be a cause of oxidative stress within tumors (6,24). In addition, tumors are frequently infiltrated by large numbers of macrophages, which have been shown to generate oxygen radicals (16). In addition, radiotherapy and photodynamic therapy generate oxygen radicals, and some chemotherapeutic agents such as cisplatin are also superoxide-generating agents (39).…”

Hydrogen peroxide mediates vascular cell adhesion molecule-1 expression from interleukin-18–activated hepatic sinusoidal endothelium: Implications for circulating cancer cell arrest in the murine liver

“…43 On the other hand, other studies have described H 2 O 2 as a relevant microenvironmental component of cancer-host cell interaction, promoting cancer cell adhesion to endothelium, invasion, and metastasis. [44][45][46] Thus, although H 2 O 2 might damage cancer cells during their dissemination, antioxidant machinery could confer to certain cancer cell subsets not only resistance to oxidative stress-mediated killing within hepatic microvasculature, but also the opportunity to progress in their metastatic process through their adhesion to HSE cells expressing VCAM-1 up-regulated by H 2 O 2 .…”