Human expression patterns: qualitative and quantitative analysis of thrombospondin‐1 under physiological and pathological conditions

Abstract

Thrombospondin‐1 (TSP‐1), a matricellular protein and one of the first endogenous anti‐angiogenic molecules identified, has long been considered a potent modulator of human diseases. While the therapeutic effect of TSP‐1 to suppress cancer was investigated in both research and clinical settings, the mechanisms of how TSP‐1 is regulated in cancer remain elusive, and the scientific answers to the question of whether TSP‐1 expressions can be utilized as diagnostic or prognostic marker for patients with cancer are largely inconsistent. Moreover, TSP‐1 plays crucial functions in angiogenesis, inflammation and tissue remodelling, which are essential biological processes in the progression of many cardiovascular diseases, and therefore, its dysregulated expressions in such conditions may have therapeutic significance. Herein, we critically analysed the literature pertaining to TSP‐1 expression in circulating blood and pathological tissues in various types of cancer as well as cardiovascular and inflammation‐related diseases in humans. We compare the secretion rates of TSP‐1 by different cancer and non‐cancer cells and discuss the potential connection between the expression changes of TSP‐1 and vascular endothelial growth factor (VEGF) observed in patients with cancer. Moreover, the pattern and emerging significance of TSP‐1 profiles in cardiovascular disease, such as peripheral arterial disease, diabetes and other related non‐cancer disorders, are highlighted. The analysis of published TSP‐1 data presented in this review may have implications for the future exploration of novel TSP‐1‐based treatment strategies for cancer and cardiovascular‐related diseases.

Fibroblast polarization over the myocardial infarction time continuum shifts roles from inflammation to angiogenesis

“…Thbs1 has been heavily implicated as a potent inhibitor of angiogenesis, mainly through pro-apoptotic and anti-VEGF actions on cardiac microvascular endothelial cells [ 71 ]. Thbs1 expression is induced in the infarcted heart by macrophages, platelets, and fibroblasts, peaking 24 h and remaining elevated as long as 28 days after MI in the rat heart [ 12 , 50 , 70 ]. Mice lacking Thbs1 show a prolonged inflammatory response and expansion of granulation tissue following MI [ 12 ].…”

Thrombospondin-1/CD47 signaling modulates transmembrane cation conductance, survival, and deformability of human red blood cells

“…Compelling molecular evidence points to an essential role for CD47-dependent TSP-1 signaling in the pathophysiology of a wide range of systemic diseases [3][4][5][6]. However, little is known about this signaling mechanism in influencing anucleate RBC functions.…”

“…Thrombospondin-1 (TSP-1), a multimodular Ca 2+ -binding trimeric matricellular glycoprotein, is secreted by a wide array of cells such as platelets, fibroblasts, macrophages, dendritic cells, vascular smooth muscle cells, keratinocytes, epithelial cells, endothelial cells, and several cancer cells [1][2][3]. Alterations in TSP-1 expression levels have been implicated in the pathophysiology of several clinical conditions including diabetes, cancer, renal failure, and cardiovascular diseases [4][5][6]. TSP-1 possesses interacting domains for a variety of proteins, which relay signals regulating a diverse range of cellular functions such as cytoskeletal organization, migration, cell-cell interaction, cell proliferation, autophagy, and apoptosis [2,7,8].…”

Soluble Intercellular Adhesion Molecule- (sICAM-) 1, Thrombospondin-1, and Vinculin for the Identification of Septic Shock Patients Suffering from an Invasive Fungal Infection

“…Thrombospondin-1 is a 129 kDa glycoprotein of the extracellular matrix with a variety of functions. Thrombospondin-1 is secreted from different cancer types [53], after tissue damage as well as in various inflammatory settings [54,55], resulting in the activation of proinflammatory macrophages [56]. Moreover, thrombospondin-1 has previously been described to play an important role in the pathogenesis of several infectious disease states, e.g., induced by Streptococcus pneumonia or Staphylococcus spp.…”