Id1 enhances human ovarian cancer endothelial progenitor cell angiogenesis via PI3K/Akt and NF-κB/MMP-2 signaling pathways.

Szczegóły
Abstrakt

Tytuł:: Id1 enhances human ovarian cancer endothelial progenitor cell angiogenesis via PI3K/Akt and NF-κB/MMP-2 signaling pathways.
Autorzy:: Su Y; Department of clinical laboratory, the affiliated tumor hospital, Harbin Medical University, Harbin, China.
Gao L
Teng L
Wang Y
Cui J
Peng S
Fu S
Źródło:: Journal of translational medicine [J Transl Med] 2013 May 29; Vol. 11, pp. 132. Date of Electronic Publication: 2013 May 29.
Typ publikacji:: Journal Article; Research Support, Non-U.S. Gov't
Język:: English
Imprint Name(s):: Original Publication: [London] : BioMed Central, 2003-
MeSH Terms:: Neovascularization, Pathologic*
Signal Transduction*
Endothelial Cells/*metabolism
Inhibitor of Differentiation Protein 1/*metabolism
Ovarian Neoplasms/*metabolism
Stem Cells/*metabolism
Adult ; Enzyme Inhibitors/pharmacology ; Female ; Gene Expression Regulation, Neoplastic ; Green Fluorescent Proteins/metabolism ; Humans ; Matrix Metalloproteinase 2/metabolism ; Middle Aged ; NF-kappa B/metabolism ; Phenotype ; Phosphatidylinositol 3-Kinases/metabolism ; Proto-Oncogene Proteins c-akt/metabolism ; RNA, Small Interfering/metabolism ; Reverse Transcriptase Polymerase Chain Reaction
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Substance Nomenclature:: 0 (Enzyme Inhibitors)
0 (ID1 protein, human)
0 (Inhibitor of Differentiation Protein 1)
0 (NF-kappa B)
0 (RNA, Small Interfering)
147336-22-9 (Green Fluorescent Proteins)
EC 2.7.1.- (Phosphatidylinositol 3-Kinases)
EC 2.7.11.1 (Proto-Oncogene Proteins c-akt)
EC 3.4.24.24 (MMP2 protein, human)
EC 3.4.24.24 (Matrix Metalloproteinase 2)
Entry Date(s):: Date Created: 20130530 Date Completed: 20131231 Latest Revision: 20211130
Update Code:: 20240104
PubMed Central ID:: PMC3687679
DOI:: 10.1186/1479-5876-11-132
PMID:: 23714001
: Czasopismo naukowe

Pełny tekst

Background: Endothelial progenitor cells (EPCs) contribute to tumor angiogenesis and growth. We previously reported that over-expression of an inhibitor of DNA binding/differentiation 1 (Id1) in EPCs can enhance EPC proliferation, migration, and adhesion. In this study, we investigated the role of Id1 in EPC angiogenesis in patients with ovarian cancer and the underlying signaling pathway.
Methods: Circulating EPCs from 22 patients with ovarian cancer and 15 healthy control subjects were cultured. Id1 and matrix metalloproteinase-2 (MMP-2) expression were analyzed by real-time reverse transcription-polymerase chain reaction (RT-PCR) and western blot. EPC angiogenesis was detected by tube formation assays. Double-stranded DNA containing the interference sequences was synthesized according to the structure of a pGCSIL-GFP viral vector and then inserted into a linearized vector. Positive clones were identified as lentiviral vectors that expressed human Id1 short hairpin RNA (shRNA).
Results: Id1 and MMP-2 expression were increased in EPCs freshly isolated from ovarian cancer patients compared to those obtained from healthy subjects. shRNA-mediated Id1 down-regulation substantially reduced EPC angiogenesis and MMP-2 expression. Importantly, transfection of EPCs with Id1 in vitro induced phosphorylation of Akt (p-Akt) via phosphoinositide 3-kinase and increased the expression of MMP-2 via NF-κB. Blockage of both pathways by specific inhibitors (LY294002 and PDTC, respectively) abrogated Id1-enhanced EPC angiogenesis.
Conclusions: Id1 can enhance EPC angiogenesis in ovarian cancer, which is mainly mediated by the PI3K/Akt and NF-κB/MMP-2 signaling pathways. Id1 and its downstream effectors are potential targets for treatment of ovarian cancer because of their contribution to angiogenesis.

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