While the overarching goal of the Tumor Microenvironment Program is to understand how extracellular cues affect tumor formation and progression, the specific goals are:
- Determine the role of and changes to the extracellular matrix (ECM) in tumor formation and progression. Included in this goal are explorations of cell adhesion and migration in response to ECM, ECM receptors and how they affect cell signaling and gene expression and changes in the deposition, composition and organization of the ECM during tumor progression.
- Understand the role of growth factors and their receptors in tumor formation and progression. Included in this goal are investigations into growth factor receptor structure, function and signaling; investigation into cross-talk between growth factor and ECM receptors; investigation of targeting growth factor pathways; and the identification of growth factor and cytokine networks that play an autocrine or paracrine role to mediate cross-talk between tumor and stromal cells.
- Explain the interplay between stromal cells and the tumor as tumors grow and progress. Stromal cells under investigation include endothelial cells and the role of angiogenesis in tumor growth, tumor intravasation and extravasation. Other cells under examination are immune cells, including macrophages, lymphocytes, NK cells and neutrophils, tumor associated macrophages which likely promote tumor progression and assist in local invasion.
A strength of combining these areas as a single group lies in the obvious synergy and interplay among them. The ECM is both derived from and affects stromal cells and growth factors and cytokines mediate the interplay between tumor and stromal cells and stimulate the deposition of ECM. As our understanding of the tumor as a complex tissue emerges, it is necessary to consider each of these in the context of the whole.