Proteomic characterization of extracellular matrix (ECM) produced by human fibroblast activation protein (FAP)-positive pericyte-like cells and glioma cells

Fibroblast activation protein (FAP) is upregulated in most cancers and represents an emerging theranostic target in oncology. In glioblastoma (GBM), FAP is predominantly expressed in mesenchymal pericyte-like cells, which contribute to GBM progression by promoting angiogenesis and glioma cell proliferation by soluble mediators. In this work, we show another possible mechanism by which these cells contribute to gliomagenesis. We observed that FAP+ pericyte-like cells residing in the perivascular niche in GBM are associated with elevated levels of the fibrillar extracellular matrix (ECM) proteins collagen I and fibronectin. Using sequential window acquisition of all theoretical mass spectra (SWATH-MS) analysis, we confirmed that the highest levels of collagen I and fibronectin are produced by FAP+ pericyte-like cells. In addition, we observed different expression pattern of basal membrane proteins between FAP+ pericyte-like cells and glioma cells.

成纤维细胞活化蛋白（Fibroblast activation protein, FAP）在多数癌症中呈高表达，是肿瘤学领域新兴的诊疗靶点。在胶质母细胞瘤（glioblastoma, GBM）中，FAP主要表达于间充质样周细胞，这类细胞可通过可溶性介质促进血管生成与胶质瘤细胞增殖，进而推动GBM进展。本研究揭示了该类细胞参与胶质瘤发生的另一潜在机制。我们观察到，GBM血管周围微环境中存在的FAP阳性样周细胞，与纤维状细胞外基质（extracellular matrix, ECM）蛋白Ⅰ型胶原及纤连蛋白的高水平表达密切相关。通过全理论质谱序列窗口采集（sequential window acquisition of all theoretical mass spectra, SWATH-MS）分析，我们证实FAP阳性样周细胞是Ⅰ型胶原与纤连蛋白的主要产生来源。此外，我们还发现FAP阳性样周细胞与胶质瘤细胞的基底膜蛋白表达模式存在差异。