Ovarian cancer (OC), the most lethal gynaecological malignancy, is the fifth leading cause of cancer-related death in women.

Despite advances in treatment, the primary challenges in overcoming ovarian cancer are relapse and metastasis.

Hence, it is crucial to mechanistically investigate relapse and metastasis and foster novel therapeutic strategies.

This research, published in the Genes & Diseases journal by a team from the Tongji University School of Medicine, Naval Military Medical University, Shanghai University School of Medicine, and Shanghai Jiaotong University School of Medicine, focuses on peritoneal adipose-derived stem cells (ADSCs), a key component of the tumour microenvironment, as significant contributors to OC metastasis.

The researchers isolated adipocytes and ADSCs from OC patients and found that ADSCs enhanced OC proliferation and migration more than adipocytes.

Notably, epidermal growth factor (EGF), a growth factor secreted by ADSCs, exhibited a significantly stronger effect on the proliferation and migration of OC cells than leptin, a major cytokine secreted by adipocytes.

Additionally, transcriptome analysis unveiled the functional importance of extracellular vesicles (EVs) in mediating long-range signalling between peritoneal ADSCs and OC cells.

The researchers found that ADSCs-EVs carried critical signalling molecules, such as EGF and epidermal growth factor receptor (EGFR), to OC cells, and upon fusion, these EVs activated key tumorigenic pathways, including the EGFR-NF-κB signalling axis, which is known to regulate inflammation, immune responses, and cancer progression.

Interestingly, the study further showed that blocking ADSCs-EVs production with a small molecule inhibitor, GW4869, or knocking down EGFR expression with shRNAs, effectively prevented the proliferation and migration of OC cells induced by ADSCs-EVs.

These findings suggest that targeting the EV-mediated communication between ADSCs and OC cells may present a promising therapeutic approach for curbing OC metastasis.

Given the complex nature and the high mortality rate associated with advanced OC, further in vivo investigations are warranted to determine the role of peritoneal ADSCs-EVs in OC progression, metastasis, and drug resistance.

In conclusion, the researchers highlight that these findings could open new avenues for the development of more effective treatments for OC by targeting the stromal cells within the peritoneal microenvironment.

Source: Compuscript Ltd