Bioluminescence imaging of fibroblast activation protein-alpha in vivo and human plasma with highly sensitive probe
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 prognos...
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| Published in | Analytical biochemistry Vol. 655; p. 114859 |
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| Main Authors | , , , , , , |
| Format | Journal Article |
| Language | English |
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Elsevier Inc
15.10.2022
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| Subjects | |
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| Abstract | 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.
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•A novel bioluminescent probe for highly sensitive detection of FAP was reported.•This probe exhibited the best selectivity, and the highest sensitivity (18.1 pg/mL).•This probe exhibited the highest signal-to-noise ratio (15000∼fold).•Quantitative measurement of FAP activity levels in plasma from gastric cancer patients for the first time. |
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| AbstractList | 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. 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. [Display omitted] •A novel bioluminescent probe for highly sensitive detection of FAP was reported.•This probe exhibited the best selectivity, and the highest sensitivity (18.1 pg/mL).•This probe exhibited the highest signal-to-noise ratio (15000∼fold).•Quantitative measurement of FAP activity levels in plasma from gastric cancer patients for the first time. 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.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. |
| ArticleNumber | 114859 |
| Author | Liu, Ling Ying, Weiwu Sheng, Zhijia Lv, Li Zhang, Ling Xue, Yunsheng Gao, Jian |
| Author_xml | – sequence: 1 givenname: Ling surname: Zhang fullname: Zhang, Ling email: zhamgling1999@163.com organization: Jiangsu Key Laboratory of New Drug Research and Clinical Pharmacy, School of Pharmacy, Xuzhou Medical University, Xuzhou, 221002, PR China – sequence: 2 givenname: Weiwu surname: Ying fullname: Ying, Weiwu organization: Jiangsu Key Laboratory of New Drug Research and Clinical Pharmacy, School of Pharmacy, Xuzhou Medical University, Xuzhou, 221002, PR China – sequence: 3 givenname: Zhijia surname: Sheng fullname: Sheng, Zhijia organization: Jiangsu Key Laboratory of New Drug Research and Clinical Pharmacy, School of Pharmacy, Xuzhou Medical University, Xuzhou, 221002, PR China – sequence: 4 givenname: Li surname: Lv fullname: Lv, Li organization: Jiangsu Key Laboratory of New Drug Research and Clinical Pharmacy, School of Pharmacy, Xuzhou Medical University, Xuzhou, 221002, PR China – sequence: 5 givenname: Jian surname: Gao fullname: Gao, Jian organization: Jiangsu Key Laboratory of New Drug Research and Clinical Pharmacy, School of Pharmacy, Xuzhou Medical University, Xuzhou, 221002, PR China – sequence: 6 givenname: Yunsheng surname: Xue fullname: Xue, Yunsheng organization: Jiangsu Key Laboratory of New Drug Research and Clinical Pharmacy, School of Pharmacy, Xuzhou Medical University, Xuzhou, 221002, PR China – sequence: 7 givenname: Ling surname: Liu fullname: Liu, Ling organization: Jiangsu Key Laboratory of New Drug Research and Clinical Pharmacy, School of Pharmacy, Xuzhou Medical University, Xuzhou, 221002, PR China |
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| Keywords | Bioluminescence imaging Probe Gastric cancer Fibroblast activation protein |
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| Title | Bioluminescence imaging of fibroblast activation protein-alpha in vivo and human plasma with highly sensitive probe |
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