Primary Culture Highlights Epithelial–Mesenchymal Interactions In Ovarian Cancer

Ovarian cancer caused 184,799 deaths (4.4%) among women in 2018 according to the International Journal of women’s health. It ranks third among gynecologic cancers with cervical and uterine cancers at the lead. The disease has a very poor prognosis and causes many deaths. This is due to a lack of early visible symptoms or screening at the early stages. This causes cancer to be detected at late stages hence getting it the name “silent killer”. The 5-year overall survival of this disease even though much research is ongoing is in the range of 30–39%, according to Parmar, Lancet, (2002).

One approach to study this cancer is the use of cell lines. It would become useful especially of the cell lines that can be propagated indefinitely in culture. This can allow studying mechanisms seen in ovarian cancer and also test therapeutic molecules. There are more than 100 human epithelial ovarian cancer (EOC) cell lines that have been generated to study this heterogeneous disease. The possibility of matching what is seen in vitro with immortalized cell lines or immunosuppressed mice models with implanted xenografts with in vivo clinical cancer gets challenging due to transformation or differences in species. Additionally, since the 1990s even though drugs plus platinum is administered to ovarian cancer patients, the care for this malady still lags behind. This calls for models that can allow detailed studies.

An article published in 2015 in Cancer Cell International by Goyeneche and team reported a primary culture from a tumor biopsy sample of a stage IIIc EOC patient. This becomes significant given that most previous works involved the culture of only ovarian cancer cells without accompanying cells. Research points out the vital roles of the accompanying cells to constitute what is referred to as “tumor microenvironment”. Hence, the long term culture was established without focusing on only one cell type.

The behavior of cells within a primary culture closely reflecting the multiple cell types in a tumor were studied. As seen with clear cell carcinoma, the majority of cells showed a clear cytoplasm. 60% of cells showed a marker called HNF1β-this protein is involved in the differentiation of the carcinoma. Another interesting finding of the primary culture was the presence of cells that were vimentin-positive and E-cadherin negative (mesenchymal phenotype) close to the epithelial cells in cancer. This is suggestive of intercellular interactions and cooperation between epithelial and mesenchymal cells referred to as epithelial-mesenchymal transition (EMT).

As carcinoma cells synthesizing DNA were observed only in the epithelial compartment but not in the mesenchymal compartment, the involvement of signals from the latter is also indicated. Another interesting finding was decreased HNF1β and an increase in mesenchymal cells over time showing a shift in cells in ovarian cancer.

Thus, primary cultures serve as invaluable tools to highlight interesting findings previously unknown in diseases such as cancer. These findings serve as avenues to design therapies with improved efficiency.

References:

Momenimovahed, Z., Tiznobaik, A., Taheri, S., &Salehiniya, H. (2019). Ovarian cancer in the world: epidemiology and risk factors. International journal of women’s health, 11, 287–299.doi:10.2147/IJWH.S197604.

Parmar MK, Ledermann JA, Colombo N, du Bois A, DelaloyeJF, et al. (2003) Paclitaxel plus platinum-based chemotherapy versus conventional platinum-based chemotherapy in women with relapsed ovarian cancer: the ICON4/AGO-OVAR-2.2 trial. Lancet 361: 2099–2106.

Goyeneche, A.A., Koch, M., Bell, M.C. et al. Long-term primary culture of a clear cell ovarian carcinoma reveals an epithelial-mesenchymal cooperative interaction. Cancer Cell International 15, 88 (2015) doi:10.1186/s12935-015-0243-8