US researchers decode origins of ovarian cancer
A team of US researchers has identified high-risk cells in fallopian tubes that may trigger a deadly form of ovarian cancer.
The discovery of the high-risk cells -- a subset of progenitor cells that reside in fallopian tube supportive tissue, or stroma -- may pave the way for better approaches to prevent and detect high-grade serous ovarian cancer (HGSOC), said the team from the University of Pittsburgh.
HGSOC is a type of ovarian cancer that starts in the fallopian tubes and spreads to the ovaries. It is the most common form of ovarian cancer.
"Ovarian cancer is a leading cause of death from gynecologic cancer, but we currently have no way to detect it early and no prevention strategies apart from surgical castration, which is only indicated in high-risk women," said Lan Coffman, Associate Professor of malignant hematology and medical oncology in the Pitt School of Medicine.
"Understanding the underlying biology of how ovarian cancer forms is critical to improving outcomes for our patients," Coffman said, in the paper, published in the journal Cancer Discovery.
HGSOC begins in the fallopian tubes when healthy epithelial cells transform into precursor lesions known as serous tubal intraepithelial carcinoma (STIC). These STIC lesions often develop into HGSOC tumours.
To find out, Coffman and her team turned to the stroma -- the non-cancerous connective tissue that helps cancer grow. In the stroma of ovarian cancer, a type of progenitor cell normally involved in the growth and repair of healthy tissue (mesenchymal stem cells (MSCs) becomes reprogrammed by tumour cells to support cancer growth.
Further probe revealed that cells that looked like cancer-associated MSCs in the fallopian tubes of healthy women, had higher risk of ovarian cancer. The risks include older age or with mutations in the BRCA gene -- suggesting that they play a role in cancer initiation.
When the researchers introduced these high-risk MSCs into organoids, or mini-organs, derived from patient fallopian tube tissue, healthy epithelial cells transformed into cancerous cells.
"High-risk MSCs promote DNA damage in epithelial cells and then help those mutated cells survive," explained Coffman. "It's the perfect storm for cancer initiation."
