Thrombospondin-1 as a Potential Therapeutic Target: Multiple Roles in Cancers

Pengfei       Wang; Zheng       Zeng; Caiji       Lin; Jiali       Wang; Wenwen       Xu; Wenqing       Ma; Qian       Xiang; Huidi       Liu; Shu-Lin       Liu
doi:10.2174/1381612826666200128091506
Abstract

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.
Keywords: Thrombospondin-1, cancer, cancer promotor, cancer suppressor, therapeutic target, active peptide, biomarker.
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DOI https://dx.doi.org/10.2174/1381612826666200128091506	Print ISSN 1381-6128
Publisher Name Bentham Science Publisher	Online ISSN 1873-4286
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