The Tumor Microenvironment (TM) Program at UW-Madison capitalizes on the involvement of many outstanding investigators whose research is focused on cell-ECM interactions, ECM structure and function, tumor cell migration and invasion, cell-cell adhesion, paracrine signaling between tumor and stromal cells, immune cell trafficking into tumors, tumor angiogenesis, metabolism, and development of in vitro models.
The TM program is clinically important because the tumor microenvironment is at the crux of metastasis and a better understanding of the mechanisms by which the microenvironment impacts tumor progression is likely to identify new ways to stratify patients and new approaches to therapy.
The overarching goal of the TM program is to understand how the interactions between the diverse elements of the tumor microenvironment affect tumor formation, progression, and response to therapy. The program will focus on three key mechanisms utilized in the tumor interactome and the translation of knowledge of the tumor microenvironment to clinical care.
Tumor and stromal cells produce and secrete growth factors, cytokines, and chemokines, which then impact other cells in the tumor microenvironment. Recent accomplishments in this area include:
- Angiogenesis: Analyzing how angiogenesis is controlled, developing model systems to study this process, and identifying methods to control angiogenesis
- Immune cells: developing systems to analyze immune cell-tumor cell interactions, harnessing the immune system for therapy
- Tumor cell response to stromal factors: determining how ECM impacts tumor cell response to soluble factors, computational modeling to analyze cell decisions, developing methods for analysis of cell signaling
Cell adhesion, migration, proliferation, and gene expression are impacted by interactions with ECM in the tumor microenvironment; tumor ECM composition and organization is in turn regulated by ECM deposition and remodeling by the tumor and stromal cells. Accomplishments in this area include:
- Analysis of ECM composition and remodeling in normal and tumor stroma
- Improved in vitro platforms to analyze role of ECM structure in the tumor microenvironment
While altered metabolism such as the Warburg Effect is a recognized hallmark of cancer, more recent studies have demonstrated that tumor cells interact with their stromal cell neighbors through the exchange of metabolic intermediates. The TM program will leverage campus investment in metabolism research to augment recent accomplishments such as:
- Understanding how the tumor microenvironment impacts metabolic reprogramming
- Investigations into the function and role of adipocytes in cancer progression
A key aspect regulating whether one patient responds to treatment while another does not is the regulation of tumor progression by the tumor microenvironment, and knowledge about the microenvironment will allow identification of patient subsets for personalized medicine. A major goal of the TM program is to continue to move studies in TM towards the clinic.
- Multiscale analysis of clinical samples
- Implantable devices for diffusion-based drug delivery/tumor sampling
- Window trial of celecoxib in patients with dense breast tissue