Low oxygen within a tumor (hypoxia) dramatically increases pulmonary metastasis and results in poor clinical outcomes. However, little is understood about the critical effects of hypoxia on sarcoma cells and the microenvironment. In this project, we are discovering how primary tumor cells respond to oxygen (O2) in their microenvironment with the goal of better understanding the spread of cancer and identifying new therapeutic targets. We have previously shown that low oxygen leads to greater deposits of the rope-like structural protein collagen in the extracellular matrix (ECM). We think that is ECM remodeling via collagen deposits impacts sarcoma cell migrate, and we hypothesize that oxygen gradients regulate the speed and direction of this migration. In vitro, in vivo and computational models are used in this project.
This project has three aims:
- To determine sarcoma cell and tumor graft responses to spatial oxygen gradients
- To characterize collagen remodeling during sarcoma invasion under hypoxic gradients
- To determine how collagen fiber organization regulates hypoxic invasion and migration
Project Leader: Sharon Gerecht
Co-Investigators: Karin Eisinger
