Ovarian carcinoma explant culture: model development and application in drug testing

Though considerable efforts have been made in the development of new tools to study ovarian cancer, currently available models are either cell line- or mouse-based. We are developing an innovative human-based model of whole explant tissue culture using primary ovarian tumors.

Recently in our laboratory, such a model has successfully been established for the study of colorectal cancer-associated liver metastasis (Halama et al. Cancer Cell 2016). Human cancer tissue is taken into culture after surgery and is viable for several days. Explants are treated with (pre-)clinical-grade drugs and subsequently processed for histological analysis as well as for multiplex cytokine analysis. This combined approach enables us to study the impact of various drugs on the tissue (in terms of tumor cell death, changes in the infiltration and activation of lymphocytes, macrophage polarization etc.).

Using this model, our ongoing project aims at characterizing the role of NIM15 in cancer. This soluble factor is highly expressed in liver metastases and ovarian primary tumors, in contrast to healthy tissues. We hypothesized that it might play a tumor-supportive role and are currently characterizing NIM15. For this, we have produced three mouse monoclonal anti-NIM15 antibodies. After explants were treated with each antibody, multiplex cytokine analysis revealed several modifications in the tumor microenvironment, such as decreased expression of several macrophage-related factors and of multiple angiogenic compounds. Various factors involved in T-cell chemotaxis were also affected. Though preliminary, these results suggest a broad effect of NIM15 and encourage us to further elucidate the role of NIM15 in cancer.