Universität zu Köln

Helfen, Anne, Hokamp, Nils Grosse, Geyer, Christiane, Heindel, Walter, Bremer, Christoph, Vogl, Thomas, Hoeltke, Carsten, Masthoff, Max, Barczyk-Kahlert, Katarzyna, Roth, Johannes, Wildgruber, Moritz and Eisenblaetter, Michel (2020). Target-Specific Imaging of Cathepsin and S100A8/A9 Reflects Specific Features of Malignancy and Enables Estimation of Tumor Malignancy. Mol. Imaging. Biol., 22 (1). S. 66 - 73. NEW YORK: SPRINGER. ISSN 1860-2002

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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.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Helfen, Anne UNSPECIFIED UNSPECIFIED UNSPECIFIED Hokamp, Nils Grosse UNSPECIFIED UNSPECIFIED UNSPECIFIED Geyer, Christiane UNSPECIFIED UNSPECIFIED UNSPECIFIED Heindel, Walter UNSPECIFIED UNSPECIFIED UNSPECIFIED Bremer, Christoph UNSPECIFIED UNSPECIFIED UNSPECIFIED Vogl, Thomas UNSPECIFIED UNSPECIFIED UNSPECIFIED Hoeltke, Carsten UNSPECIFIED UNSPECIFIED UNSPECIFIED Masthoff, Max UNSPECIFIED UNSPECIFIED UNSPECIFIED Barczyk-Kahlert, Katarzyna UNSPECIFIED UNSPECIFIED UNSPECIFIED Roth, Johannes UNSPECIFIED UNSPECIFIED UNSPECIFIED Wildgruber, Moritz UNSPECIFIED UNSPECIFIED UNSPECIFIED Eisenblaetter, Michel UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-347271
DOI:	10.1007/s11307-019-01370-1
Journal or Publication Title:	Mol. Imaging. Biol.
Volume:	22
Number:	1
Page Range:	S. 66 - 73
Date:	2020
Publisher:	SPRINGER
Place of Publication:	NEW YORK
ISSN:	1860-2002
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language CANCER; INNATE Multiple languages Radiology, Nuclear Medicine & Medical Imaging Multiple languages
URI:	http://kups.ub.uni-koeln.de/id/eprint/34727