Journal article
Selective imaging of solid tumours via the calcium-dependent high-affinity binding of a cyclic octapeptide to phosphorylated Annexin A2
Nature biomedical engineering, Vol.4(3), pp.298-313
03/2020
DOI: 10.1038/s41551-020-0528-7
PMID: 32165732
Abstract
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.
Details
- Title: Subtitle
- Selective imaging of solid tumours via the calcium-dependent high-affinity binding of a cyclic octapeptide to phosphorylated Annexin A2
- Creators
- Duanwen Shen - Washington University in St. LouisBaogang Xu - Washington University in St. LouisKexian Liang - Washington University in St. LouisRui Tang - Washington University in St. LouisGail P Sudlow - Washington University in St. LouisChristopher Egbulefu - Washington University in St. LouisKevin Guo - Washington University in St. LouisAvik Som - Washington University in St. LouisRebecca Gilson - Washington University in St. LouisDolonchampa Maji - Washington University in St. LouisSuman Mondal - Washington University in St. LouisLeMoyne Habimana-Griffin - Department of Biomedical Engineering, Washington University, St. Louis, MO, 63110, USAWalter Akers - Washington University in St. LouisShunqiang Li - Washington University in St. LouisYang Liu - Washington University in St. LouisSharon Bloch - Washington University in St. LouisSid Kurkure - Washington University in St. LouisZohar Nussinov - Washington University in St. LouisAlexander Seidel - Washington University in St. LouisShaw-Wei D Tsen - Department of Radiology, Washington University, St. Louis, MO, 63110, USASamuel Achilefu - Department of Radiology, Washington University, St. Louis, USA
- Resource Type
- Journal article
- Publication Details
- Nature biomedical engineering, Vol.4(3), pp.298-313
- DOI
- 10.1038/s41551-020-0528-7
- PMID
- 32165732
- NLM abbreviation
- Nat Biomed Eng
- ISSN
- 2157-846X
- eISSN
- 2157-846X
- Grant note
- DOI: 10.13039/100000002, name: U.S. Department of Health & Human Services | National Institutes of Health, award: R01 CA171651, U54 CA199092
- Language
- English
- Date published
- 03/2020
- Academic Unit
- Electrical and Computer Engineering
- Record Identifier
- 9984197534602771
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