Dendritic cells support angiogenesis and promote lesion growth in a murine model of endometriosis.
Endometriosis affects 10-15% of women and is associated with pelvic pain and infertility. Angiogenesis plays an essential role in its pathogenesis. Dendritic cells (DCs) were recently implicated in supporting tumor angiogenesis. As both tumors and endometriosis lesions depend on angiogenesis, we investigated the possibility that DCs may also play a role in endometriosis. We induced endometriosis in 8-wk-old female C57BL/6 mice by implantation of autologous endometrium into the peritoneal cavity. We observed an abundance of CD11c(+) DCs infiltrating sites of angiogenesis in endometriosis lesions. We noticed a similar pattern of infiltrating DCs at sites of angiogenesis in the peritoneal Lewis lung carcinoma tumor model. These DCs were immature (major histocompatability complex class II(low)) and expressed vascular endothelial growth factor receptor 2. Peritoneal implanted bone marrow-derived DCs (BMDCs) incorporated into both endometriosis lesions and into B16 melanoma tumors and enhanced their growth at 8 days compared with controls (5.1+/-2.5 vs. 1.5+/-0.5 mm(2), n=4 and 4, P<0.0001 for endometriosis; 67.6+/-15.1 vs. 22.7+/-14.6 mm(2), n=5 and 7, P=0.0004 for mouse melanoma). Finally, immature BMDCs but not mature BMDCs enhanced microvascular endothelial cell migration in vitro (219+/-51 vs. 93+/-32 cells, P=0.02). Based on these findings, we suggest a novel role for DCs in supporting angiogenesis and promoting lesion growth both in endometriosis and in tumors.
Fainaru
Ofer
O
Vascular Biology Program, Children's Hospital Boston, Harvard Medical School, 300 Longwood Ave., Boston, MA 02115, USA. ofer.fainaru@childrens.harvard.edu
Adini
Avner
A
Benny
Ofra
O
Adini
Irit
I
Short
Sarah
S
Bazinet
Lauren
L
Nakai
Kei
K
Pravda
Elke
E
Hornstein
Mark D
MD
D'Amato
Robert J
RJ
Folkman
Judah
J
D000818:Animals; D002454:Cell Differentiation; D002465:Cell Movement; D017690:Cell Transplantation; D002478:Cells, Cultured; D003713:Dendritic Cells / Q000166:cytology / Q000378:metabolism / Q000637:transplantation; D004195:Disease Models, Animal; D004715:Endometriosis / Q000473:pathology*; D042783:Endothelial Cells / Q000473:pathology; D005260:Female; D008175:Lung Neoplasms / Q000473:pathology; D008545:Melanoma / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D009389:Neovascularization, Pathologic / Q000473:pathology*; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000378:metabolism
D040301:Vascular Endothelial Growth Factor Receptor-2