Expression von SDF-1/CXCL12 und CXCR4 in der sequenziellen DMBA-induzierten Karzinogenese des Hamsters

Expression of SDF-1/CXCL12 and CXCR4 in the sequentially DMBA induced carcinogenesis in a hamster model

by Eva Nadenau
Doctoral thesis
Date of Examination:2015-03-16
Date of issue:2015-03-31
Advisor:Prof. Dr. Dr. Henning Schliephake
Referee:Prof. Dr. Nicolai Miosge
Referee:Prof. Dr. Rainer Mausberg
Persistent Address: http://dx.doi.org/10.53846/goediss-4940

 

 

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Abstract

English

Mutual communication between chemokine stromal-derived-factor 1 (SDF-1/CXCL12) and the corresponding receptor CXCR4 may influence the motility, the tendency toward invasive growth, and the mode of metastasis of tumor cells. This study evaluates and assesses the expression of SDF-1/CXCL12 and CXCR4 in correlation to the histological findings in an animal experiment. It was hypothesized that the expression of SDF-1/ CXCL12 and CXCR4 is regulated. In the animal study with the previously described set-up of the DMBA-induced buccal pouch cancer in the hamster, different stages of mucosal dysplasia where induced by different periods of DMBA application. In 40 biopsies of healthy mucosa, dysplastic altered mucosa and different modes of differenciated squamous cell carcinoma, the expression of SDF-1/CXCL12 and CXCR4 was assessed with immuno-histologic methods and compared to the histologic findings of the HE-stained specimens. CXCR4 was found in healthy mucosa, dysplatic altered mucosa and in squamous cell carcinoma, regardless of the histological findings. The expression of SDF-1/CXCL 12 correlated significantly with the histological findings. While the expression of this factor was limited to the stratum basale in healthy mucosa, the expression in dysplasic altered mucosa was unorganized and found through out all areas of the epithelium. In squamous cell carcinomas no expression of SDF-1/CXCL 12 was found in any stages of differentiation. In the “DMBA-induced buccal pouch cancer in the hamster experiment” the existence of a regulation of the des SDF- 1/CXCL12-CXCR4-dependend signal transduction system was proven, in particular because of an expression of SDF-1/CXCL12 that was not limited to the stratum basale in a regular way, but in contrast was found beyond that border through out all areas to the epithelium.
Keywords: CXCL12; CXCR4; CXCL12/ CXCR4; DMBA induced Carcinogenesis; expression of CXCL12 CXCR4; oral cancer
Schlagwörter: Plattenepithelkarzinom; CXCL12 CXCR4; DMBA induzierte Karzinogenese; Expression CXCL12 CXCR4
 
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