TY - JOUR
T1 - Dendritic cell subsets differentially regulate angiogenesis in human ovarian cancer
AU - Curiel, Tyler J.
AU - Cheng, Pui
AU - Mottram, Peter
AU - Alvarez, Xavier
AU - Moons, Lieve
AU - Evdemon-Hogan, Melina
AU - Wei, Shuang
AU - Zou, Linhua
AU - Kryczek, Ilona
AU - Hoyle, Gary
AU - Lackner, Andrew
AU - Carmeliet, Peter
AU - Zou, Weiping
N1 - Copyright:
Copyright 2008 Elsevier B.V., All rights reserved.
PY - 2004/8/15
Y1 - 2004/8/15
N2 - Angiogenesis is essential for both primary and metastatic tumor growth. Tumor blood vessel formation is complex and regulated by many factors. Ovarian carcinomas have a poor prognosis, often associated with multifocal intraperitoneal dissemination accompanied by intense neovascularization. To examine tumor angiogenesis in the tumor microenvironment, we studied malignant ascites of patients with untreated ovarian carcinoma. We observed high numbers of plasmacytoid dendritic cells (PDCs) and significant stromal-derived factor (CXCL-12/SDF)-1 in their malignant ascites, attracting PDCs into the tumor environment. We now show that tumor-associated PDCs induced angiogenesis in vivo through production of tumor necrosis factor a and interleukin 8. By contrast, myeloid dendritic cells (MDCs) were absent from malignant ascites. MDCs derived in vitro suppressed angiogenesis in vivo through production of interleukin 12. Thus, the tumor may attract PDCs to augment angiogenesis while excluding MDCs to prevent angiogenesis inhibition, demonstrating a novel mechanism for modulating tumor neovascularization. Because dendritic cells (DCs) have long been known to affect tumor immunity, our data also implicate DCs in regulation of tumor neoangiogenesis, suggesting a novel role of DCs in tumor pathology.
AB - Angiogenesis is essential for both primary and metastatic tumor growth. Tumor blood vessel formation is complex and regulated by many factors. Ovarian carcinomas have a poor prognosis, often associated with multifocal intraperitoneal dissemination accompanied by intense neovascularization. To examine tumor angiogenesis in the tumor microenvironment, we studied malignant ascites of patients with untreated ovarian carcinoma. We observed high numbers of plasmacytoid dendritic cells (PDCs) and significant stromal-derived factor (CXCL-12/SDF)-1 in their malignant ascites, attracting PDCs into the tumor environment. We now show that tumor-associated PDCs induced angiogenesis in vivo through production of tumor necrosis factor a and interleukin 8. By contrast, myeloid dendritic cells (MDCs) were absent from malignant ascites. MDCs derived in vitro suppressed angiogenesis in vivo through production of interleukin 12. Thus, the tumor may attract PDCs to augment angiogenesis while excluding MDCs to prevent angiogenesis inhibition, demonstrating a novel mechanism for modulating tumor neovascularization. Because dendritic cells (DCs) have long been known to affect tumor immunity, our data also implicate DCs in regulation of tumor neoangiogenesis, suggesting a novel role of DCs in tumor pathology.
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U2 - 10.1158/0008-5472.CAN-04-1272
DO - 10.1158/0008-5472.CAN-04-1272
M3 - Article
C2 - 15313886
AN - SCOPUS:4143064951
VL - 64
SP - 5535
EP - 5538
JO - Cancer Research
JF - Cancer Research
SN - 0008-5472
IS - 16
ER -