Characteristics and differentiated mechanism of vascular endothelial cells-like derived from epithelial ovarian cancer cells induced by hypoxia.
A few highly aggressive and malignant tumor cells could acquire identities by turning on genes expressed by endothelial cells and recruit blood vessels to sustain tumor growth. Hypoxia was reported recently to play an essential role in these events. These 'plastic' tumor-cell phenotypes and the exact mechanism driving transendothelial differentiation by hypoxia-inducible factor (HIF)-1alpha is unclear. In this study, epithelial ovarian carcinoma cells were exposed to hypoxia and the tumor cells were transformed into endothelial cells-like (ECs-like). Typical endothelial features such as cell markers and uptaking of acetylated low density lipoprotein were identified constantly. Small interference RNA was used to block the expression of HIF-1alpha. Analysis revealed that hypoxia promotes transendothelial differentiation through stimulating HIF-1-dependent transcriptional expression of vascular endothelial growth factor (VEGF), VEGF receptor-2 (Flk-1) and P53, and through decreasing HIF-1-independent transcriptional expression of Cyclin D1. These results demonstrate that ECs-like derived from epithelial ovarian cancer cells are similar to endothelial progenitor cells rather than endothelial cells. HIF-1alpha is crucial but not unique in alternation of tumor cells towards ECs-like.
Yao
Liang-Qing
LQ
Department of Gynecologic Oncology, Obstetrics and Gynecology Hospital, Fudan University, Shanghai, PR China.
Feng
You-Ji
YJ
Ding
Jing-Xin
JX
Jing
Hui-Ming
HM
Xu
Cong-Jian
CJ
Chen
Si-Feng
SF
Su
Ming
M
Yin
Liang-Hua
LH
D002454:Cell Differentiation; D019938:Cyclin D1 / Q000378:metabolism; D042783:Endothelial Cells / Q000166:cytology*; D004730:Endothelium, Vascular / Q000473:pathology*; D004847:Epithelial Cells / Q000166:cytology*; D005260:Female; D006801:Humans; D000860:Hypoxia; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000378:metabolism; D008856:Microscopy, Fluorescence; D010051:Ovarian Neoplasms / Q000378:metabolism*; D034741:RNA, Small Interfering / Q000378:metabolism; D014407:Tumor Cells, Cultured / Q000166:cytology; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000378:metabolism
C497442:HIF1A protein, human; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D034741:RNA, Small Interfering; D016159:Tumor Suppressor Protein p53; D019938:Cyclin D1; D040301:Vascular Endothelial Growth Factor Receptor-2