Department of Biomedical Sciences, University of Guelph, Guelph, ON, Canada.
Department of Biomedical Sciences, University of Guelph, Guelph, ON, Canada.
Semin Cell Dev Biol. 2024 Mar 1;155(Pt B):3-11. doi: 10.1016/j.semcdb.2023.05.010. Epub 2023 Jun 5.
Many cancers begin with the formation of a small nest of transformed cells that can remain dormant for years. Thrombospondin-1 (TSP-1) initially promotes dormancy by suppressing angiogenesis, a key early step in tumor progression. Over time, increases in drivers of angiogenesis predominate, and vascular cells, immune cells, and fibroblasts are recruited to the tumor mass forming a complex tissue, designated the tumor microenvironment. Numerous factors, including growth factors, chemokine/cytokine, and extracellular matrix, participate in the desmoplastic response that in many ways mimics wound healing. Vascular and lymphatic endothelial cells, and cancer-associated pericytes, fibroblasts, macrophages and immune cells are recruited to the tumor microenvironment, where multiple members of the TSP gene family promote their proliferation, migration and invasion. The TSPs also affect the immune signature of tumor tissue and the phenotype of tumor-associated macrophages. Consistent with these observations, expression of some TSPs has been established to correlate with poor outcomes in specific types of cancer.
许多癌症始于一小群转化细胞的形成，这些细胞可以休眠多年。血小板反应蛋白-1（TSP-1）最初通过抑制血管生成来促进休眠，血管生成是肿瘤进展的关键早期步骤。随着时间的推移，血管生成的驱动因素增加，血管细胞、免疫细胞和成纤维细胞被招募到肿瘤块中，形成一个复杂的组织，称为肿瘤微环境。许多因素，包括生长因子、趋化因子/细胞因子和细胞外基质，参与了在许多方面模拟伤口愈合的促结缔组织反应。血管和淋巴管内皮细胞以及癌相关周细胞、成纤维细胞、巨噬细胞和免疫细胞被招募到肿瘤微环境中，TSP 基因家族的多个成员促进它们的增殖、迁移和侵袭。TSP 还影响肿瘤组织的免疫特征和肿瘤相关巨噬细胞的表型。与这些观察结果一致，某些 TSP 的表达已被确定与特定类型癌症的不良预后相关。
