HPV in 3D organoids
Cervical cancer (CC) is the second most commonly occurring cancer in women in South Africa. The major etiological factor for developing CC is a persistent infection with high-risk Human Papillomavirus (HPV) strain; particularly HPV16 which is associated with >75% of all cases. The virus infects the ectocervix via the activity of viral oncoproteins E6 and E7, which dysregulate cellular processes involved in apoptosis, cell division, differentiation and growth. Uncontrolled cellular proliferation is induced, leading to CC. How HPV-induced cancer starts is poorly understood, particularly in a South African context, so we need to develop a reliable disease model to conduct further research on this malignancy.
In the field of CC research, there are limited models available, all with their own pitfalls. Cell lines experience genetic drift, patient-derived xenografts only offer translational information, and spheroids are made up of only one cell type. In trying to marry the positive attributes of all of these models while mitigating their drawbacks, patient-derived organoids were used. This study created patient-derived ectocervical organoids and transduced them with lentiviral particles containing HPV16 oncogenes E6 and E7 in order to mimic an in vivo infection and subsequent carcinogenesis. Early viral oncogenesis was successfully initiated in the transduced organoids, altering the proteomic and transcriptomic profile of the organoids. These newly-created organoids mirror a malignant profile (i.e. they appear to look and act like early cancer, so that we are able to study the CC in detail).
Project team:
- Prof Mandeep Kaur (School of Molecular and Cell Biology, Wits)
- Ms Naaziyah Abdulla (PhD 足球竞彩app排名, School of Molecular and Cell Biology, Wits)
- Ms Katharine Dirks (MSc 足球竞彩app排名, School of Molecular and Cell Biology, Wits)
- Dr Langanani Mbodi (Gynaecologic Oncology Unit, Wits; Chris Hani Baragwanath Academic Hospital)