Organoids give insight into the development of cervical cancer

Molecular changes that give rise to cervical cancer have been identified using novel 'organoid' models.

Published in Nature Cell Biology, researchers in Germany have developed an organoid model of the cervix, providing them with a unique way to study its normal biology and better understand why cancers develop.

'These fundamental findings form a basis for further understanding of the mechanisms involved in carcinogenesis at these metaplastic sites. To study how human papillomavirus (HPV), together with superseding bacterial infections, plays a key role in transforming cells to malignancy,' said Dr Cindrilla Chumduri from the Biocentre at the University of Würzburg, who led the study.

Organoids are tiny 3D structures made of cells – just a few millimetres in size – that are artificially developed to closely resemble whole organs. They are increasingly used in medical research to allow scientists to study life processes and the effect of drugs.

Prior to this new study, it was known that the cervix has two regions covered by two different types of epithelial cells – so called 'squamous epithelia' and 'columnar epithelia'. The boundaries between these two different cell types are called transition zones, and 90 perecent of cervical cancers originate at these sites. However, it was not known exactly how these two cell populations – and their boundaries – are ordinarily kept distinct in a healthy cervix, or why this is a hotspot for cancer development.

Using the organoid structures, the researchers discovered that instead of the two different epithelial cell types developing from the same stem cells, they are in fact derived from two discrete stem cell populations.

Complex interactions between these stem cells and their surrounding microenvironment were found to be important for keeping the two types of cells separate and for ensuring a healthy cervical architecture. This is achieved using the Wnt signaling pathway – proteins known for their role in cellular differentiation, among other processes.

The researchers also showed that disrupting Wnt signalling can alter the homeostasis seen in the cervix, allowing one type of epithelium cell to replace the other – an early event in cancer development termed metaplasia. Different types of cervical cancers can develop depending on which epithelial cell population is displaced.

It is hoped that this improved understanding of the fundamental biology of the cervix and the molecular changes seen in cervical metaplasia will help improve our understanding of how certain viral and bacterial infections – principally HPV – cause cervical cancer.

Dr Chumduri also added, 'these critical insights can help to develop diagnostics for the early detection of these two tumour forms and new therapeutic strategies'.