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Target-Specific Imaging of Cathepsin and S100A8/A9 Reflects Specific Features of Malignancy and Enables Estimation of Tumor Malignancy
- Source :
- Molecular Imaging and Biology. 22:66-72
- Publication Year :
- 2019
- Publisher :
- Springer Science and Business Media LLC, 2019.
-
Abstract
- Tumor development and metastasis are dependent on tumor infiltrating immune cells which form a characteristic tumor microenvironment (TME). Activated monocytes secrete the protein heterodimer S100A8/A9 promoting TME formation. Monocyte-dependent proteases facilitate local tumor cell invasion by degradation of the extracellular matrix. We aimed for target specific in vivo imaging of S100A8 and proteases to provide differentiating biomarkers for local tumor growth and metastatic potential. Murine breast cancer cells of the 4T1 model with graduated metastatic potential (4T1 and 4T07: both hematogenous metastasis > 168FAR: lymph-node metastasis > 67NR: no metastasis) were orthotopically implanted into female BALB/c mice. At 4 mm size, tumors were investigated by injecting the protease-specific probe ProSense 750EX (PerkinElmer, 4T1 n = 7, 4T07 n = 10, 168FAR n = 16, 67NR n = 15) and anti-S100A8-Cy5.5 (n = 6 each) and performing fluorescence reflectance imaging at 0 and 24 h after injection. In vivo imaging was validated with immunohistochemistry. At 24 h, S100A8-specific signals in 4T1 and 4T07 were significantly higher (1714.05/1683.45 AU) as compared to 168FAR and 67NR (174.85/167.95 AU, p = 0.0012/p = 0.0003), reflecting the capability of hematogenous spread. Protease-specific signals were significantly higher in 4T1 and 4T07 (348.01/409.93 AU) as compared to 168FAR (214.91 AU) and 67NR (129.78 AU p
- Subjects :
- Cancer Research
Proteases
Mammary Neoplasms, Animal
Malignancy
030218 nuclear medicine & medical imaging
Metastasis
Extracellular matrix
Mice
03 medical and health sciences
0302 clinical medicine
Immune system
Cell Line, Tumor
Tumor Microenvironment
Animals
Medicine
Calgranulin A
Radiology, Nuclear Medicine and imaging
Neoplasm Staging
Mice, Inbred BALB C
Tumor microenvironment
business.industry
Optical Imaging
Carbocyanines
medicine.disease
Cathepsins
Immunohistochemistry
Molecular Imaging
Disease Models, Animal
Oncology
Cancer research
Female
business
Preclinical imaging
Subjects
Details
- ISSN :
- 18602002 and 15361632
- Volume :
- 22
- Database :
- OpenAIRE
- Journal :
- Molecular Imaging and Biology
- Accession number :
- edsair.doi.dedup.....28f4754953c99bb92e56584055b2b254