Thrombospondin-1 anti-angiogenic signaling in endothelial cells

Thrombospondin-1 anti-angiogenic signaling in endothelial cells

Thrombospondin-1 (TSP-1) is a key anti-angiogenic extracellular matrix protein that is down-regulated in many tumors. It has however multiple receptors on the cell surface – CD36, CD47, and beta1-integrin among others – and its mechanism of action is highly debated.

The goal of this project is to investigate the dynamics and cross-interactions between its multiple receptors in order to shed light on the mechanism(s) of TSP-1 signaling. We are interested in questions such as:

  • Do these receptors work separately or together?
  • Do they support or antagonize each other?
  • Are they needed simultaneously or separately under different conditions?

In collaboration with the Touret lab at the University of Alberta, Edmonton, we have started investigating the role of CD36, one of the TSP-1 receptors. Initial results implicate a close relationship between CD36 and beta1-integrin. Thus, next we would like to investigate the role of beta1-integrin in more detail, then CD47, etc.