Reactive oxygen species and melanoma: an explanation for gender differences in survival?

Abstract

SummaryEpidemiological research consistently shows a female advantage in melanoma survival. So far, no definite candidate for the explanation of this phenomenon has emerged. We propose that gender differences in oxidative stress caused by radical oxygen species (ROS) underlie these survival differences. It is known that males express lower amounts of anti-oxidant enzymes, resulting in more oxidative stress than females. The primary melanoma environment is characterized by high ROS levels, from exogenous sources as well as ROS production within melanoma cells themselves. ROS are known to be able to promote metastasis through a wide variety of mechanisms. We hypothesize that the higher levels of ROS in men enhance selection of ROS-resistance in melanoma cells. Subsequently, ROS can stimulate the metastatic potential of melanoma cells. In addition, due to the lower anti-oxidant defenses in men, ROS produced by melanoma cells cause more damage to healthy tissues surrounding the tumor, further stimulating metastasis. Therefore, ROS may explain the observed differences between males and females in melanoma survival.

The Polysaccharide Extracted from <i>Umbilicaria esculenta</i> Inhibits Proliferation of Melanoma Cells through ROS-Activated Mitochondrial Apoptosis Pathway

“…As a key factor in regulating cellular homeostasis, ROS also plays a significant role in various pathological processes such as tumor development, apoptosis and metastasis. 22) Previous research has shown that elevated intracellular ROS levels in a certain range could promote melanoma metastasis, [23][24][25] whereas excessive ROS could induce tumor cell damage and apoptosis through a wide variety of mechanisms. 26) In this study, we tested the level of ROS in A875 melanoma cells after treatment of PUE, and the result that the ROS level in A875 melanoma cells detected by flow cytometry significantly increased in a dose-dependent manner, which demonstrated that high level of ROS in treated melanoma cells could be induced by PUE.…”

Effect of biology on the outcome of female melanoma patients

“…Numerous other factors were hypothesized to be possible explanations for the survival advantage of female melanoma patients, such as oxidative stress, drugs and ethanol consumption (5,20). Men are known to express lower amounts of antioxidant enzymes; therefore, they may produce a higher level of radical oxygen species, thus enhancing metastasis via multiple pathways.…”

“…In order to explain this difference, researchers have suggested two major hypotheses so far: The first hypothesis is based on behavioral characteristics, such as that men have more advanced disease at diagnosis due to certain lifestyle characteristics (i.e., men are exposed to the sun more often and for longer periods compared with women, and are less conscious of skin care and skin cancer, thus not taking sufficient preventive measures) that may result in delays in screening, detection and diagnosis of the disease (4). The second hypothesis is that there is a biological trait that has yet to be elucidated, which accounts for the sex-related survival difference in melanoma; this unclear biological trait is believed to be associated with either the tumor per se (namely, the disease in female patients is naturally less aggressive), or with factors within the host (namely, female sex prevents disease progression and spread) (5)(6)(7)(8)(9).…”

“…The first hypothesis was controverted and the second hypothesis was advocated by the fact that the female survival advantage persisted even following adjustment for factors such as Breslow's thickness, and that lymph node and visceral organ metastases did not affect the higher survival rate of female patients (4,(5)(6)(7)(8)(9)(10)(11). Thus, it was concluded that the aggressiveness of the disease did not affect the survival benefit of female melanoma patients.…”

Targeting Adenosine Receptors for the Treatment of Melanoma

“…ROS could also induce expression of cell adhesion molecules on the primary tumor cells and endothelial cells which could promote the metastatic process. In support of these findings, a number of in vivo studies in experimental animals demonstrated that antioxidants/antioxidant enzymes were effective in lowering the metastatic potential of melanoma cells (for review, see Joosse et al, 2010). However, all antioxidants/antioxidant enzymes were not effective.…”