Abstract SY04-01: Skin stem cells in silence, action, and cancer

Abstract

Abstract Stem cells have the ability to self-renew long term and differentiate into one or more tissues. Typically, stem cells are used sparingly to replenish cells during normal homeostasis. This is particularly true of adult tissues which undergo relatively infrequent or periodic turnover. However, stem cells must also have the ability to respond quickly in response to injury, where they must be mobilized to undergo rapid tissue regeneration. How stem cells balance self-renewal and differentiation is of fundamental importance to our understanding of normal tissue maintenance and wound repair. Moreover, increasing evidence suggests that the regulatory circuitry governing this balancing act is at the root of some types of tumors both in mice and in humans. The skin is an excellent model system to understand how stem cells function in normal tissue generation and how this process goes awry in cancer. Using skin as our paradigm, we've been dissecting how extrinsic signaling to stem sets off a cascade of changes in transcription that governs the activation of stem cells during tissue development, homeostasis and hair regeneration. Our findings have provided us with new insights into our understanding of the process of stem cell activation, and in so doing have revealed mechanisms which are also deregulated in a variety of different human cancers. As importantly in understanding how stem cells are activated is learning about the signals that instruct stem cells to stop making tissue. Our recent discoveries on this topic have led us to the realm of identifying cancer stem cells (tumor-initiating cells) of squamous cell carcinomas of the skin. The second most abundant form of cancer world-wide, skin squamous cell carcinomas also establish a paradigm for many life-threatening cancers of lung, esophagus, breast, cervix, prostate, throat and oral tissues. We've demonstrated that when purified and introduced directly into the skin of a host recipient, a single cancer stem cell from a skin squamous cell carcinoma can generate a new squamous cell carcinoma that is similar in properties to the parent tumor. We show that cancer stem cell numbers and aggressiveness are predicated on the tumor microenvironment and on the ability of cancer stem cells to respond to it. The striking differences between the microenvironments of cancer stem cells and their normal counterparts seems likely to contribute to why their expression profiles are also markedly distinct. Our findings have major implications for our understanding of stem cells and cancer. [This work was supported by the HHMI and grants from the National Institutes of Health and The Emerald Foundation] Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr SY04-01. doi:1538-7445.AM2012-SY04-01