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01-02-2020 | Metastasis | Brief Article

Target-Specific Imaging of Cathepsin and S100A8/A9 Reflects Specific Features of Malignancy and Enables Estimation of Tumor Malignancy

Authors: Anne Helfen, Nils Große Hokamp, Christiane Geyer, Walter Heindel, Christoph Bremer, Thomas Vogl, Carsten Höltke, Max Masthoff, Katarzyna Barczyk-Kahlert, Johannes Roth, Moritz Wildgruber, Michel Eisenblaetter

Published in: Molecular Imaging and Biology | Issue 1/2020

Abstract

Purpose

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.

Procedures

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.

Results

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 < 0.0001 each), reflecting local vessel invasion and tumor cell shedding. Immunohistology supported the in vivo imaging results.

Conclusions

Non-invasive in vivo imaging of S100A8 and monocytic proteases allows for differentiation of the tumors’ local invasive and systemic metastatic potential in reflecting the TME formation. While proteases augment local tumor cell invasion, solid metastases seem to be dependent on a pro-tumoral microenvironment.

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Title: Target-Specific Imaging of Cathepsin and S100A8/A9 Reflects Specific Features of Malignancy and Enables Estimation of Tumor Malignancy
Authors: Anne Helfen
Nils Große Hokamp
Christiane Geyer
Walter Heindel
Christoph Bremer
Thomas Vogl
Carsten Höltke
Max Masthoff
Katarzyna Barczyk-Kahlert
Johannes Roth
Moritz Wildgruber
Michel Eisenblaetter
Publication date: 01-02-2020
Publisher: Springer International Publishing
Keywords: Metastasis
Molecular Imaging
Published in: Molecular Imaging and Biology / Issue 1/2020
Print ISSN: 1536-1632
Electronic ISSN: 1860-2002
DOI: https://doi.org/10.1007/s11307-019-01370-1

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Target-Specific Imaging of Cathepsin and S100A8/A9 Reflects Specific Features of Malignancy and Enables Estimation of Tumor Malignancy

Abstract

Purpose

Procedures

Results

Conclusions

Keynote webinar | Spotlight on sleep in brain health

Springer Medicine

Abstract

Purpose

Procedures

Results

Conclusions

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