TY - JOUR
T1 - Selective imaging of solid tumours via the calcium-dependent high-affinity binding of a cyclic octapeptide to phosphorylated Annexin A2
AU - Shen, Duanwen
AU - Xu, Baogang
AU - Liang, Kexian
AU - Tang, Rui
AU - Sudlow, Gail P.
AU - Egbulefu, Christopher
AU - Guo, Kevin
AU - Som, Avik
AU - Gilson, Rebecca
AU - Maji, Dolonchampa
AU - Mondal, Suman
AU - Habimana-Griffin, Le Moyne
AU - Akers, Walter J.
AU - Li, Shunqiang
AU - Liu, Yang
AU - Bloch, Sharon
AU - Kurkure, Sid
AU - Nussinov, Zohar
AU - Seidel, Alexander
AU - Tsen, Shaw Wei D.
AU - Achilefu, Samuel
N1 - Publisher Copyright:
© 2020, The Author(s), under exclusive licence to Springer Nature Limited.
PY - 2020/3/1
Y1 - 2020/3/1
N2 - The heterogeneity and continuous genetic adaptation of tumours complicate their detection and treatment via the targeting of genetic mutations. However, hallmarks of cancer such as aberrant protein phosphorylation and calcium-mediated cell signalling provide broadly conserved molecular targets. Here, we show that, for a range of solid tumours, a cyclic octapeptide labelled with a near-infrared dye selectively binds to phosphorylated Annexin A2 (pANXA2), with high affinity at high levels of calcium. Because of cancer-cell-induced pANXA2 expression in tumour-associated stromal cells, the octapeptide preferentially binds to the invasive edges of tumours and then traffics within macrophages to the tumour’s necrotic core. As proof-of-concept applications, we used the octapeptide to detect tumour xenografts and metastatic lesions, and to perform fluorescence-guided surgical tumour resection, in mice. Our findings suggest that high levels of pANXA2 in association with elevated calcium are present in the microenvironment of most solid cancers. The octapeptide might be broadly useful for selective tumour imaging and for delivering drugs to the edges and to the core of solid tumours.
AB - The heterogeneity and continuous genetic adaptation of tumours complicate their detection and treatment via the targeting of genetic mutations. However, hallmarks of cancer such as aberrant protein phosphorylation and calcium-mediated cell signalling provide broadly conserved molecular targets. Here, we show that, for a range of solid tumours, a cyclic octapeptide labelled with a near-infrared dye selectively binds to phosphorylated Annexin A2 (pANXA2), with high affinity at high levels of calcium. Because of cancer-cell-induced pANXA2 expression in tumour-associated stromal cells, the octapeptide preferentially binds to the invasive edges of tumours and then traffics within macrophages to the tumour’s necrotic core. As proof-of-concept applications, we used the octapeptide to detect tumour xenografts and metastatic lesions, and to perform fluorescence-guided surgical tumour resection, in mice. Our findings suggest that high levels of pANXA2 in association with elevated calcium are present in the microenvironment of most solid cancers. The octapeptide might be broadly useful for selective tumour imaging and for delivering drugs to the edges and to the core of solid tumours.
UR - http://www.scopus.com/inward/record.url?scp=85081171473&partnerID=8YFLogxK
U2 - 10.1038/s41551-020-0528-7
DO - 10.1038/s41551-020-0528-7
M3 - Article
C2 - 32165732
AN - SCOPUS:85081171473
SN - 2157-846X
VL - 4
SP - 298
EP - 313
JO - Nature Biomedical Engineering
JF - Nature Biomedical Engineering
IS - 3
ER -