Sid B, Sartelet H, Bellon G, El Btaouri H, Rath G, Delorme N, Haye B, Martiny L
Laboratoire de Biochimie, UFR Sciences de Reims, FRE-CNRS 2534, IFR 53 "Biomolécules", Moulin de la housse BP1039, 51687 Reims Cedex 2, France.
Crit Rev Oncol Hematol. 2004 Mar;49(3):245-58. doi: 10.1016/j.critrevonc.2003.09.009.
Thrombospondins belong to a family of extracellular matrix (ECM) proteins widely found from embryonic to adult tissues. The modular structure of thrombospondins contains a series of peptide sequences implicated in a multiplicity of biological functions. Extracellular matrix undergoes important alterations under proteolysis that occurs in pathological processes like tumorigenesis. An elevated secretion of thrombospondin 1 (TSP1) is often observed in tumors and is sometimes considered as a predictive factor. However, the role of TSP1 in cancer progression remains controversial and must be carefully apprehended. The regulation of cell adhesion, proliferation, apoptosis by TSP1 is examined in the present review and it is clear from the literature and from our investigations that TSP1 presents both stimulatory and inhibitory effects. The exposition of cryptic sites upon conformational changes can partially explain this contradiction. More interestingly, the analysis of TSP1-directed intracellular signaling pathways activated through specific receptors or supramolecular receptors docking systems may be useful to discriminate the precise function of TSP1 in tumor progression. The central role played by TSP1 in the control of matrix-degrading enzyme activation and catabolism reveals attractive tracks of research and highlights the involvement of the lipoprotein receptor-related protein (LRP) receptor in these events. Therefore, TSP1-derived peptides constitute a source of potentially active matrikins which could provide essential tools in cancer therapy.
血小板反应蛋白属于细胞外基质（ECM）蛋白家族，广泛存在于从胚胎到成人的组织中。血小板反应蛋白的模块化结构包含一系列与多种生物学功能相关的肽序列。细胞外基质在蛋白水解作用下会发生重要改变，这种蛋白水解作用发生在肿瘤发生等病理过程中。在肿瘤中经常观察到血小板反应蛋白1（TSP1）的分泌增加，有时它被视为一个预测因素。然而，TSP1在癌症进展中的作用仍存在争议，必须谨慎理解。本综述研究了TSP1对细胞黏附、增殖、凋亡的调节作用，从文献和我们的研究中可以清楚地看到，TSP1具有刺激和抑制两种作用。构象变化时隐蔽位点的暴露可以部分解释这种矛盾。更有趣的是，分析通过特定受体或超分子受体对接系统激活的TSP1导向的细胞内信号通路，可能有助于区分TSP1在肿瘤进展中的精确功能。TSP1在控制基质降解酶激活和分解代谢中所起的核心作用揭示了有吸引力的研究方向，并突出了脂蛋白受体相关蛋白（LRP）受体在这些事件中的参与。因此，TSP1衍生的肽构成了潜在活性基质分子的来源，这可能为癌症治疗提供重要工具。
