Laboratory of Tumor Microenvironment, Department of Oncology, Istituto di Ricerche Farmacologiche Mario Negri IRCCS, Via Stezzano 87, Bergamo 24126, Italy.
Laboratory of Tumor Microenvironment, Department of Oncology, Istituto di Ricerche Farmacologiche Mario Negri IRCCS, Via Stezzano 87, Bergamo 24126, Italy.
Semin Cell Dev Biol. 2024 Mar 1;155(Pt B):45-51. doi: 10.1016/j.semcdb.2023.06.009. Epub 2023 Jul 4.
Thrombospondins (TSPs) have numerous different roles in cancer, regulating the behavior of cancer cells and non-neoplastic cells, and defining the responses of tumor cells to environmental changes, thorough their ability to orchestrate cellular and molecular interactions in the tumor microenvironment (TME). As a result of these activities, TSPs can also control drug delivery and activity, tumor response and resistance to therapies, with different outcomes depending on the nature of TSP-interacting cell types, receptors, and ligands, in a highly context-dependent manner. This review, focusing primarily on TSP-1, discusses the effects of TSPs on tumor response to chemotherapy, antiangiogenic, low-dose metronomic chemotherapy, immunotherapy, and radiotherapy, by analyzing TSP activity on different cell compartments - tumor cells, vascular endothelial cells and immune cells. We review evidence of the value of TSPs, specifically TSP-1 and TSP-2, as biomarkers of prognosis and tumor response to therapy. Finally, we examine possible approaches to develop TSP-based compounds as therapeutic tools to potentiate the efficacy of anticancer therapy.
血栓反应蛋白（TSPs）在癌症中有多种不同的作用，通过调节癌细胞和非肿瘤细胞的行为，并通过协调肿瘤微环境（TME）中的细胞和分子相互作用来定义肿瘤细胞对环境变化的反应，从而发挥作用。由于这些活动，TSPs 还可以控制药物的递送和活性、肿瘤的反应和对治疗的耐药性，具体结果取决于 TSP 相互作用的细胞类型、受体和配体的性质，这是一种高度依赖于上下文的方式。这篇综述主要集中在 TSP-1 上，通过分析 TSP 在不同细胞区室（肿瘤细胞、血管内皮细胞和免疫细胞）上的活性，讨论了 TSPs 对化疗、抗血管生成、低剂量节拍化疗、免疫治疗和放射治疗的肿瘤反应的影响。我们回顾了 TSPs（特别是 TSP-1 和 TSP-2）作为预后和肿瘤对治疗反应的生物标志物的价值的证据。最后，我们研究了开发基于 TSP 的化合物作为治疗工具以增强抗癌治疗效果的可能方法。
