Evaluation der Interaktionen zwischen extrazellulärer Matrix und ausgewählten tumorassoziierten Proteinen mittels Nahinfrarot-Antikörpern

Evaluation of interactions between the extracellular matrix and selected tumor-associated proteins with near-infrared antibodies

by Jan-Niklas Eckardt
Doctoral thesis
Date of Examination:2020-10-29
Date of issue:2020-10-23
Advisor:Dr. Jeannine Missbach-Güntner
Referee:Prof. Dr. Frauke Alves
Referee:Prof. Dr. Freddy Wouters-Bunt
Persistent Address: http://dx.doi.org/10.53846/goediss-8263

 

 

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Abstract

English

The interplay between tumor cells and their microenvironment is crucial for carcinogenesis and tumor progression. In my thesis, I examine selected tumor-associated proteins that interact with the extracellular matrix surrounding tumor cells by evaluating their interactions with selected antibodies that are conjugated to near-infrared fluorophors (NIRF) in vitro and in vivo. I demonstrate an identical pattern of biodistribution of NIRF-antibodies independent of tumor model, tumor transplantation mode in vivo, conjugated fluorophore and temporal dynamics. Further, in a two-dimensional in vitro model I demonstrate the upregulation of a selected tumor-associated protein in response to chemotherapy with concomitant cell lysis whereas in a three-dimensional model chemotherapy selected a more aggressive phenotype of tumor cells clearly underlining distinct differences between different dimensional models in cell culture.
Keywords: Extracellular Matrix; EpCAM; Lysyloxidase; CD44; Tumor Spheroid; Near-Infrared Antibody
 
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