Mini versions of mouse reproductive organs have been used to investigate how the most lethal ovarian cancers develop.
Up to 80 percent of ovarian cancer mortalities are caused by high-grade serous ovarian cancer (referred to here as just 'ovarian cancer'), which is usually not diagnosed until a late stage. This means that early development of the cancer is not well characterised.
Researchers at the Hubrecht Institute in Utrecht, the Netherlands, developed tumour progression models from mouse tissue. They used their models to study the origins of ovarian cancer and found two sites that can give rise to tumours, but that one of the sites more readily formed malignancies. Those involved in the research believe this work is important because knowing more about the development and progression of ovarian cancer may help doctors to better recognise ovarian cancer in the future.
The team grew organoids of the mouse oviducts (equivalent to human fallopian tubes) and ovarian surface epithelium (the outer layer of the ovaries). These organoids are artificially grown 'mini versions' of parts of the mouse reproductive organs. They then used CRISPR/Cas9 genome editing to mutate genes Trp53, Brca1, Nf1 and Pten, which are already known to mutate in ovarian cancer.
After mutation, the organoids were transplanted back into mice, and developed into tumours that were similar to those found in human ovarian cancer. However, tumours were more prone to develop from the oviduct organoids than the ovarian surface epithelium organoids. The oviduct organoids also grew into larger, faster-developing tumours.
The novel method of combining organoids and CRISPR/Cas9 was previously developed by the same group (see BioNews 918), and has recently been used to investigate COVID-19 (see BioNews 1046). Organoids have also been used to study other types of cancer.
The organoid models used in the study, published in Nature Communications, can help scientists to understand how malignancies such as ovarian cancer develop, potentially allowing for earlier treatment, and greater survival rates.