Thrombospondin-1, an extracellular matrix protein, is the first identified natural angiogenesis inhibitor.
Thrombospondin-1 participates in a great number of physiological and pathological processes, including cell-cell
and cell-matrix interactions via a number of cell receptors, including CD36 and CD47, which plays a vital role in
mediating inflammation and performs a promoting effect in pulmonary arterial vasculopathy and diabetes.
Thrombospondin-1 consists of six domains, which combine with different molecules and participate in various
functions in cancers, serving as a critical member in diverse pathways in cancers. Thrombospondin-1 works as a
cancer promotor in some pathways but as a cancer suppressor in others, which makes it highly possible that its
erroneous functioning might lead to opposite effects. Therefore, subdividing the roles of thrombospondin-1 and
distinguishing them in cancers are necessary. Complex structure and multiple roles take disadvantage of the research
and application of thrombospondin-1. Compared with the whole thrombospondin-1 protein, each thrombospondin-
1 active peptide performs an uncomplicated structure and, nevertheless, a specific role. In other words,
various thrombospondin-1 active peptides may function differently. For instance, thrombospondin-1 could both
promote and inhibit glioblastoma, which is significantly inhibited by the three type I repeats, a thrombospondin-1
active peptide but promoted by the fragment 167-569, a thrombospondin-1 active peptide consisting of the procollagen
homology domain and the three type I repeats. Further studies of the functions of thrombospondin-1
active peptides and applying them reasonably are necessary. In addition to mediating cancerogenesis,
thrombospondin-1 is also affected by cancer development, as reflected by its expression in plasma and the cancer
tissue. Therefore, thrombospondin-1 may be a potential biomarker for pre-clinical and clinical application. This
review summarizes findings on the multiple roles of thrombospondin-1 in cancer processes, with a focus on its
use as a potential therapeutic target.