In response to: 14-CA-102 Understanding the Heterogeneity of Cancer and its Environment. Assembly and disassembly of stromal architecture in the tumor microenvironment. Frank Marini- UTM.D. Anderson Cancer Center To meet the requirements for rapid tumor growth, a complex array of non-neoplastic vascular, fibroblastic, and immune cells are recruited into the tumor microenvironment to provide structural, vascular, and paracrine support. Understanding the origin and composition of these stromal elements will help identify potential targets for therapeutic intervention that deprive the tumor of nutritional and/or structural requirement. Our proposed studies aim at understanding the role of various stromal elements in the tumor microenvironment and elucidate the contribution of MSC in generation of tumor-associated stroma. By using a two pronged approach of multicolor cellular transplant, and by utilizing a novel multi-reporter gene transgenic animal (the "rainbow" stroma mouse) generated by us to evaluate and understand the complex dynamic interactions of tumor and stromal components in vivo. This mouse possesses fluorescently labeled cells and multiple colored bone marrow resident precursor populations: (LacZ-labeled endothelial progenitor (Tie2 promoter), GFP-labeled myeloid progenitors (cFMS-promoter), YFP-bone marrow fibroblasts/mesenchyme (FSP1-promoter) known to participate in tumor stroma formation. Transplanted tumors developing in the rainbow mouse recruit labeled cell populations, as tumor structural elements that originate from gene marked populations will be surveyed, identified, and quantitated. Objective/hypothesis: We hypothesize that stromal precursor elements originate from bone marrowand fat-derived progenitor populations and are recruited to form tumor stroma and this recruitment is mediated through CD44.

PUBLIC HEALTH RELEVANCE: Tumor growth is reliant on other cells of the body to produce supportive stroma, without stroma a tumor will stop growing. We have uncovered that a normal stem cell population, called mesenchymal stem cells (MSC) play a key role in tumor stroma formation, and their recruitment into the tumor. This project relates to the better understanding of why MSC are recruited to tumors and provides a rationale for potentially targeting stroma as a method to control or eliminate tumor growth.

RC1CA146381

2009-09-30

2012-08-31