Jiangsu Key Laboratory of New Drug Research and Clinical Pharmacy, School of Pharmacy, Xuzhou Medical University, Xuzhou, 221002, PR China; State Key Laboratory of Coordination Chemistry, Nanjing University, Nanjing, 210023, PR China.
Jiangsu Key Laboratory of New Drug Research and Clinical Pharmacy, School of Pharmacy, Xuzhou Medical University, Xuzhou, 221002, PR China.
Anal Biochem. 2022 Oct 15;655:114859. doi: 10.1016/j.ab.2022.114859. Epub 2022 Aug 18.
Fibroblast activation protein-alpha (FAPα) has emerged as a biomarker of tumor stromal fibroblasts. FAP was overexpressed in stromal fibroblasts of human malignancies and positively correlated with the depth of tumor invasion, lymphatic metastasis, distant metastases, high TNM stage and poor prognosis. However, the circulating FAP levels in the plasma of gastric cancer patients and the relationship between FAP levels and gastric cancer remain unknown. Moreover, probes with super selectivity, extremely high sensitivity, and excellent performance in quantitative detection are still lacking. Herein, we developed the bioluminescent probe BL-FAP for sensitive detection and imaging of endogenous FAP in gastric cancer cells and tissues and plasma from gastric cancer patients. The probe exhibited the high signal-to-noise ratio (15000∼fold), the excellent selectivity (FAP/DPP IV ratio and FAP/PREP ratio = 50000∼ fold), and the high sensitivity (18.1 pg/mL). BL-FAP facilitates monitoring of endogenous FAP in living cells and nude mice bearing MGC-803-luc tumors. More importantly, this probe was successfully applied to the measurement of FAP activity levels in plasma from gastric cancer patients for the first time. A significant enhancement in FAP levels was observed in patients with gastric cancer, suggesting that the FAP level may be a potential diagnostic parameter for gastric cancer.
成纤维细胞激活蛋白-α（FAPα）已成为肿瘤基质成纤维细胞的生物标志物。FAP 在人类恶性肿瘤的基质成纤维细胞中过度表达，与肿瘤侵袭深度、淋巴转移、远处转移、高 TNM 分期和预后不良呈正相关。然而，胃癌患者血浆中的循环 FAP 水平以及 FAP 水平与胃癌之间的关系尚不清楚。此外，还缺乏具有超高选择性、极高灵敏度和出色定量检测性能的探针。在此，我们开发了用于灵敏检测和成像胃癌细胞和组织以及胃癌患者血浆中内源性 FAP 的生物发光探针 BL-FAP。该探针具有高信噪比（15000∼倍）、出色的选择性（FAP/DPP IV 比和 FAP/PREP 比= 50000∼倍）和高灵敏度（18.1 pg/mL）。BL-FAP 有利于监测活细胞和携带 MGC-803-luc 肿瘤的裸鼠中的内源性 FAP。更重要的是，该探针首次成功应用于测量胃癌患者血浆中的 FAP 活性水平。在胃癌患者中观察到 FAP 水平显著升高，表明 FAP 水平可能是胃癌的潜在诊断参数。
