Cancer cells purged from human ovarian tissue fragments by pharmacological inhibition of YAP/TAZ oncoproteins
A new paper published in Human Reproduction March 2019 helps to solve the question as to whether it is possible to eliminate metastasized cancer cells from ovarian cortex fragments prior to auto transplantation – without compromising the tissue or follicles. In ex vivo experiments pharmacological inhibition of YAP/TAZ enabled the team from Radboud University, The Netherlands, to eradicate from human ovarian tissue fragments induced small tumours. This research is important because auto transplantation of ovarian tissue fragments containing tumour cells could reintroduce malignancy to the recipient.
Human ovarian tissue was obtained after female-to-male sex reassignment surgery and human rhabdomyosarcoma, leukaemia, breast cancer and Ewing’s sarcoma cell lines were used to induce tumour foci. The tissue fragments were cultured to allow formation of metastasis-like structures followed by a 24 hours ex vivo treatment to eradicate cancer cells. Rhabdomyosarcoma and leukaemia cells were effectively purged from the cortex tissue but breast cancer and Ewing’s sarcoma did not respond. Ovarian tissue integrity seemed not affected by purging and no statistically significant difference was observed in the percentage of morphologically normal follicles, percentage of follicles with apoptotic cells, follicular viability or glucose uptake between the control treated ovarian cortex and Verteporfin treated ovarian cortex.
The results of the study, funded in part by Merck B.V., seems to show that ex-vivo tumour cell purging of ovarian cortex fragments for fertility preservation is feasible and helps the safety of ovarian cortex auto-transplantation, increasing the chances that this form of fertility restoration could become an option for patients with malignancies where ovarian cortex transplantation is currently considered unsafe. The team, led by Dr Callista Mulder, are unclear whether the results reflect the behaviour of malignant cells that have metastasized to the ovary during natural disease progression and suggest that the functionality of the ovarian tissue after ex vivo treatment requires further investigation in vivo.
For further information
Enhancing the safety of ovarian cortex autotransplantation: cancer cells are purged completely from human ovarian tissue fragments by pharmacological inhibition of YAP/TAZ oncoproteins
Callista L Mulder Lotte L Eijkenboom Catharina C M Beerendonk Didi D M Braat Ronald Peek
Human Reproduction, Volume 34, Issue 3, March 2019, Pages 506–518
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