Geburtshilfe Frauenheilkd 2020; 80(10): e222-e223
DOI: 10.1055/s-0040-1718225
Poster
Mittwoch, 7.10.2020
Gynäkologische Onkologie IV

Three-dimensional tumor spheroid models to investigate tumor-stroma-interactions under the influence of the tumorsuppressor gene ITIH5

S George
1   Department of Gynaecology and Reproductive Medicine, Jena University Hospital, Friedrich-Schiller-University, Jena, Deutschland
,
L Jansen
1   Department of Gynaecology and Reproductive Medicine, Jena University Hospital, Friedrich-Schiller-University, Jena, Deutschland
,
W Weigand
2   Institute of Inorganic and Analytical Chemistry, Friedrich-Schiller-University, Jena, Deutschland
,
IB Runnebaum
1   Department of Gynaecology and Reproductive Medicine, Jena University Hospital, Friedrich-Schiller-University, Jena, Deutschland
,
M Dürst
1   Department of Gynaecology and Reproductive Medicine, Jena University Hospital, Friedrich-Schiller-University, Jena, Deutschland
,
C Backsch
1   Department of Gynaecology and Reproductive Medicine, Jena University Hospital, Friedrich-Schiller-University, Jena, Deutschland
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Objective Human papillomavirus-induced cervical carcinogenesis is accompanied by various epi(genetic) alterations. Of particular relevance is the progressive downregulation of the gene ITIH5. Previous functional in vitro analyses using conventional cell culture provide further evidence of ITIH5 possessing tumor suppressive properties. Aim of the current study is the investigation of tumor-stroma-interactions under the influence of ITIH5 (with and without cytostatics) using cervical carcinoma cell-specific three-dimensional (3D) tumor spheroid models (including co-culture models).

Materials To generate cell culture models, ITIH5 was ectopically overexpressed in the cervical carcinoma cells SiHa and ME180 using retroviral transduction. For co-culture models primary fibroblasts are additionally used.

Methods These cell lines and their co-cultures are used to generate multicellular tumor spheroids via the hanging-drop method. Immunohistochemical analyses and ELISA are carried out to determine expression of various extracellular matrix components, including MMP2 and MMP9. Proliferation assays are performed as well as cytotoxicity assays using various routinely used cytostatic drugs and novel cytostatic agents.

Results Functionally, ITIH5 overexpression significantly suppressed tumor spheroid growth and invasiveness in SiHa and ME180 spheroids. Thus far, SiHa ITIH5-overexpressed and co-cultured cells have a tendencially reduced release of MMP9 and elevated release of MMP2. In ME180 ITIH5-overexpressed and co-cultured cells we found a slightly increased MMP2 and MMP9 release. All investigations are ongoing.

Summary Possible effects of ITIH5 itself, on tumor-stroma interactions as well as on chemotherapy of cervical carcinoma cell lines using 3D tumorspheroid models may provide a new approach for individualized therapy of cervical cancer in the future.



Publication History

Article published online:
07 October 2020

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