Regulation of Angiogenesis and Tumor Growth by Thrombospondin-1

Thrombospondin-1 (TSP-1) is a matricellular protein that has been implicated in playing an important role in inhibiting cancer progression. Many studies have been carried out to characterize the mechanism of its action. While its ability to inhibit tumor angiogenesis through binding of CD36 via the thrombospondin type 1 repeats (TSRs) sequence have been well studied, the long-range effect of TSP-1’s ability to activate transforming growth factor β (TGF-β) is just starting to be characterized. One such effect is shifting the balance of the fibrinolytic system through TSP-1’s ability to inhibit matrix metalloproteinases and plasminogen activator inhibitor-1. A shift in either direction could promote tumor progression, including metastasis, or prevent it by reducing tumor angiogenesis. This delicate balance may be responsible for the conflicting data in the literature on whether TSP-1 is proor antitumorigenic, and the direction of the shift may also be cell-type specific. Lastly, the potential of developing a TSP-based therapy is being realized and clinical trials are now underway.