Chronic inflammation: is it the driver or is it paving the road for malignant transformation?
Kambiz Afrasiabi1, Yi-Hong Zhou2, Angela Fleischman1
1 Department of Medicine, University of California, Irvine, CA, USA
2 Department of Surgery, University of California, Irvine, CA, USA
Correspondence:
Kambiz Afrasiabi, email:
Keywords: Chronic inflammation, Free energy, driver mutation, bioenergetics, metabolomics, electric field and cancer, JAK2V617F, p53 Rb
Received: March 17, 2015 Accepted: May 7, 2015 Published: May 8, 2015
Abstract
Chronic inflammation in well-defined mouse models such as Giα2 knock out mouse has been shown to trigger formation and expansion of hypoxic niches and also leads to up regulation of NFĸB, offering cells which have adapted their genetic machinery to hypoxia a unique survival advantage. These adapted cells have been shown to acquire stem cell-like capabilities as shown by up regulation of stem cell markers. Such long lived cells become permanent residents in sub mucosa and acquire a malignant phenotype from long-term exposure to noxious environmental agents due to a barrier defect secondary to down regulation of barrier proteins such as Zo1 and Occludin. Indeed mitotic spindle disorientation in such mice has been proposed as another contributory factor to malignant transformation. Sterilization of bowel lumen of these mice through different techniques has prevented malignant transformation in the presence of chronic inflammation. These facts stand strongly against chronic inflammation as a true driver of carcinogenesis but clearly support its role in facilitating the emergence of the neoplastic clone.
