Dendritic cells have been caught red handed for supporting angiogenesis that may lead to endometriosis.
Almost every woman has retrograde menstruation, the suspected root of endometriosis, but usually the immune system digests tissue that has regressed through the fallopian tubes and into the peritoneal cavity.
Ofer Fainaru, HMS research fellow in the Vascular Biology Program at Children’s Hospital Boston, and his colleagues wanted to learn why endometriosis occurs in 10 to 15 percent of women and how the condition could be interrupted. “If there is a problem in immune cell function, the shed endometrial tissue is not cleared from the peritoneal cavity, and it implants, vascularizes, and grows,” Fainaru said.
Fainaru completed his research in the lab of Judah Folkman, the Julia Dyckman Andrus professor of pediatric surgery at HMS and CHB and the study’s senior author. Folkman is credited with discovering that cancer tumors are generally angiogenesis-dependent. Endometriosis implants share this dependency.
“These implants are behaving very much like tumors in the way that they induce their own vascularization,” said Fainaru, lead author of the murine study, which was published online in FASEB Journal on Sept. 14 and will appear in the February print edition.
Fainaru and his colleagues surgically induced endometriosis in mice and detected significant angiogenesis eight days later. Analysis of the lesions showed they were infiltrated with immature dendritic cells, expressing the angiogenic marker vascular endothelial growth factor receptor 2 (VEGFR-2). By expressing VEGFR-2, a receptor normally expressed on endothelial cells, which line blood vessels, the dendritic cells may shift to a proangiogenic role, which is uncommon for immune cells.
“We showed that by implanting dendritic cells into the peritoneal cavity, they were incorporated into the lesions and caused the lesions to grow and become more vascularized,” Fainaru said.
He and his colleagues compared these findings with cancer angiogenesis using a mouse melanoma tumor model and saw similar results. The injected dendritic cells caused enhanced tumor growth and increased angiogenesis when compared to controls.
Although there is some controversy about whether dendritic cells actually incorporate into tumor vessel walls, as reported in a 2004 study in Nature Medicine, or whether they are strategically placed around the vessels, the cells significantly contribute to the process of angiogenesis, Fainaru said.
The current treatment for endometriosis involves surgical removal of the implants and hormonal suppression thereafter, but the painful condition often recurs. Fainaru next plans to ablate dendritic cells locally in his murine model to learn if endometriosis is dependent on these cells. If it is, he envisions treating the immune cells locally in the peritoneal cavity, thereby blocking or otherwise disrupting the progression of angiogenesis and endometriosis itself.
