Cell finding brings hope for uterus ailments

Dec 27 2019

Associate Professor Pradeep Tanwar with fellow researchers Dr Dariusz Alterman, left, and Dr Shafiq Syed.

Researchers from the University of Newcastle and Hunter Medical Research Institute (HMRI) believe they have solved a 75-year scientific mystery by pinpointing a cell that’s behind a raft of health conditions affecting the uterus, including endometrial cancer, endometriosis and infertility.

With a genetic signal known as Axin2, the cell primarily sparks the rapid regeneration of the womb lining (endometrium) after menstruation, according to lead researcher Associate Professor Pradeep Tanwar.

However, it also appears to fuel uterine illnesses when the cell becomes dysfunctional or mutated, and potentially undermines the success of IVF. The finding therefore has potential to create several new treatment models.

Associate Professor Tanwar and his team spent seven years exhaustively testing their discovery, first made in 2012, and have just published the results in the prestigious journal Cell Stem Cell.

“We’ve known since 1944 that the epithelium [of the uterus] is shed during menses then renewed within a week, but no one has understood quite how it happens,” Associate Professor Tanwar says.

“Many groups predicted bone marrow-derived cells were responsible, and there are trials using these cells in women, but our [pre-clinical] testing has shown that it’s the Axin2 cell of the endometrium.”

The Tanwar team collected and banked gynaecological tissue samples from hundreds of women in the Hunter Region while also developing new laboratory models to prove their finding.

As part of their investigations, they labelled the Axin2 cell with a genetic dye and discovered it was principally responsible for the development of endometrial cancer, the most common form of gynaecological cancer which is escalating due to obesity and other lifestyle factors.

“Other endometrial cells might mutate as well, but this is the dominant cell type – like the queen bee in a nest,” Associate Professor Tanwar confirms. “These are also the cells that might leak out of the uterus and cause endometriosis.

“We found that inhibiting the cell stops the uterine regeneration process. If we inhibit it in cancer, the cancer won’t progress. Nor will endometriosis, we believe, so our next step is to develop clinical applications … looking for existing drugs that can be repurposed.”

Endometriosis impacts 700,000 women in Australia, with the painful condition often requiring multiple surgeries and affecting fertility in more than 30 per cent of cases. Around 3000 women are diagnosed with uterine cancer each year, tragically resulting in more than 500 deaths. Less than 18 per cent of IVF cycles result in a live birth.

The study was supported by a NHMRC Career Development Fellowship and HMRI through the Dorothy Jean Cunningham Endometrial Cancer Research Bequest.

* A/Professor Tanwar is a NHMRC Career Development Fellow from the University of Newcastle, researching in conjunction with HMRI’s Cancer Program. HMRI is a partnership between the University of Newcastle, Hunter New England Health and the community.