Role of 4-hydroxynonenal in communication between cancer stem cells and microenvironment

Cancer stem cells are a subpopulation of cancer cells with great plasticity, slow cell cycle and are capable of dormating for long time. Today, these cells are recognized as a major factor of malignancy causing metastasis, relapse, failure of cancer treatment and therapy resistance. The mechanisms which keep in control or activate these cells are still not fully revealed, but microenvironment certainly has a specific role. Proteins of the extracellular matrix can modify proccesses which cells are undergoing and changes of these proteins consequently affect cell. In addition to the environmental signals, oxidative stress may modulate and change signals cells are recieving thereby creating different outcome. Among the molecules produced during oxidative stress, 4-hydroxynonenal (HNE) was shown to modulate many signaling pathways thereby inducing differentiation, proliferation or apoptosis. Here, we provide evidence that HNE can change cancer stem cell responce to chronic oxidative stress through interactions with collagen, representative of extracellular matrix protein. Hence, HNE may be the factor that modulates cellular responce to stress or therapy via interactions with extracellular proteins and thereby changing the outcome of the disease.