Ovarian Microenvironment
Research type
Research Study
Full title
Biological Properties and Alterations of the Tumour Microenvironment Governing Ovarian Cancer Progression (OCM)
IRAS ID
234389
Contact name
Angela Shone
Contact email
Sponsor organisation
University of Nottingham
Duration of Study in the UK
10 years, 0 months, 31 days
Research summary
Research Summary:
Ovarian cancer is often described as an “inflammatory” cancer. This means that the tumour and the surrounding immune cells produce signals normally used by the body to fight infection but in this setting, those signals may actually help the cancer survive and spread.
One important inflammation pathway is controlled by something called the NLRP3 inflammasome. This acts like a molecular alarm system inside immune cells. When switched on, it leads to the release of inflammatory molecules such as interleukin-1β (IL-1β). These molecules are useful when fighting infections, but in cancer they may create a harmful environment that supports tumour growth and resistance to treatment.
In this project, we studied samples of ovarian cancer taken directly from patients, particularly from omental metastases (tumour deposits in fatty tissue inside the abdomen). We tested whether this inflammatory “alarm system” could be activated in these tissues outside the body and whether blocking it might reduce inflammatory signalling.
We found that:
Ovarian cancer tissue from patients showed evidence of active inflammatory signalling.
The NLRP3 pathway could be strongly activated in patient-derived samples.
Blocking a related receptor (called P2X7) reduced the release of inflammatory molecules.
Importantly, earlier laboratory studies using cancer cell lines alone showed very little activity in this pathway. Our findings suggest that the wider tumour environment plays a major role in driving inflammation in real patient tissue.
Overall, this work suggests that targeting inflammatory pathways such as NLRP3 or P2X7 could represent a future therapeutic strategy in ovarian cancer. While more research is needed, these findings help us better understand how inflammation contributes to disease progression and may open the door to new treatment approaches. We consider it essential to study inflammatory processes in patient‑derived samples rather than in cell lines
The human ovary is a unique organ, one that is important for regulating reproduction, hormone balance, bone turnover and fertilisation. As a result it is supplied by a rich supply of chemical messengers and as such undergoes significant changes in tissue makeup both in pre and post-menopausal life. Ovarian cancer is a disease of poorly understood origin and limited information exists about the process through which normal cells are transformed to a cancerous state. Although it is only the second most common gynaecological cancer it has the highest mortality rate, due to the fact the approximately 70% of women are diagnosed at an advanced stage of the disease. Therefore further research is required not only to improve the outcomes of women with ovarian cancer but to further understand the contribution of biological factors in the ovarian environment to the development and advancement of the disease. We suggest that the role of local biological factors such as acid concentrations and bioelectric signals within the ovary are pivotal in the development of ovarian cancer and in the poor response to treatment regimes in place. Our research will focus on changes in the local environment of the ovary and ovarian cancer especially proteins that transport signals across cell membranes and how they respond to key factors within the ovary. The discovery of new processes involved in ovarian cancer development will open up new opportunities. It is hoped that this study will shed new light on an increasing problem that affects many women and may help in the longer term to improve ovarian cancer outcomes and propose new treatment approaches that are not centred on killing cancer cells and the associated negative side effects of chemotherapy.
REC name
East Midlands - Leicester South Research Ethics Committee
REC reference
17/EM/0453
Date of REC Opinion
1 Dec 2017
REC opinion
Favourable Opinion