Abstract CN08-02: Implications of the cancer stem cell hypothesis for breast cancer prevention

Abstract

Abstract The cancer stem cell hypothesis proposes that cancers arise in cell populations that either dysregulate or acquire the stem cell property of self-renewal. Resulting cancers are hierarchically organized and driven by a subpopulation that retains stem cell properties. This suggests that dysregulation of self-renewal plays an important role in early stages of carcinogenesis and that an understanding of the pathways which regulate self-renewal may lead to new strategies for cancer prevention. Our laboratory has identified markers including CD44+/CD24- and Aldehyde dehydrogenase which have proven useful in identifying populations of normal and transformed breast epithelial cells. Furthermore, we have developed in vitro and animal models to elucidate pathways which regulate self-renewal in these cells. These studies, and others, suggest that stem cell self-renewal is regulated by an interaction of intrinsic and extrinsic pathways. Intrinsic regulation occurs through interacting developmental pathways including Notch, hedgehog, Wnt and Akt. Cytokine networks in the stem cell niche including IL-8 and IL6 also play important roles in stem cell regulation. These pathways may also contribute to the well-known links between inflammation and cancer. Inflammatory cytokines may contribute to clonal expansion of stem cell populations which can then acquire secondary genetic changes resulting in expression of the fully malignant phenotype. We have demonstrated that dietary components including curcumin and sulforaphane which have been shown to have chemopreventive properties are able to target Wnt signaling in stem cell populations. These and other studies support the approach of targeting stem cell self-renewal pathways for cancer prevention.