RGD Reference Report - Activation of multiple angiogenic signaling pathways in hemangiopericytoma. - Rat Genome Database

Send us a Message



Submit Data |  Help |  Video Tutorials |  News |  Publications |  Download |  REST API |  Citing RGD |  Contact   

Activation of multiple angiogenic signaling pathways in hemangiopericytoma.

Authors: Pierscianek, Daniela  Michel, Anna  Hindy, Nicolai El  Keyvani, Kathy  Dammann, Philipp  Oezkan, Neriman  Mueller, Oliver  Sure, Ulrich  Zhu, Yuan 
Citation: Pierscianek D, etal., Brain Tumor Pathol. 2016 Jul;33(3):200-8. doi: 10.1007/s10014-016-0256-6. Epub 2016 Mar 7.
RGD ID: 155663351
Pubmed: PMID:26951238   (View Abstract at PubMed)
DOI: DOI:10.1007/s10014-016-0256-6   (Journal Full-text)

Hemangiopericytoma (HPC) is a highly vascularized mesenchymal tumor. Local recurrence and distant metastasis are common features of HPC. Considering the remarkable hyper-vasculature phenotype of HPC, we assumed that dysregulated angiogenic signaling pathways were involved in HPC. The key components of angiogenic signaling pathways including VEGF-VEGF-R2, EphrinB2-EphB4 and DLL4-Notch were examined by real-time RT-PCR, Western blotting and immunostaining in 17 surgical specimens of HPC patients and in 6 controls. A significant upregulation of VEGF and VEGF-R2 associated with elevated levels of p-Akt and proliferating cell nuclear antigen (PCNA) was detected in HPC. Moreover, a dramatic increase in the mRNA and protein expression of EphB4 and its downstream factor p-Erk1/2 was found in HPC. A massive activation of core-components of DLL4-Notch signaling was detected in HPC. Double-immunofluorescent staining confirmed the expression of these upregulated key factors in the endothelial cells of tumor vessels. The present study identified the activation of multiple and crucial angiogenic signaling pathways, which could function individually and/or synergistically to stimulate angiogenesis in HPC and eventually contribute to tumor growth and progression. Our findings emphasize the importance to target multiple angiogenic signaling pathways when an anti-angiogenic therapy is considered for this highly vascularized tumor.



RGD Manual Disease Annotations    Click to see Annotation Detail View

  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
DLL4Humanhemangiopericytoma  IEP mRNA and protein:increased expression:anterior temporal lobeRGD 
Dll4Rathemangiopericytoma  ISODLL4 (Homo sapiens)mRNA and protein:increased expression:anterior temporal lobeRGD 
Dll4Mousehemangiopericytoma  ISODLL4 (Homo sapiens)mRNA and protein:increased expression:anterior temporal lobeRGD 
EPHB4Humanhemangiopericytoma  IEP mRNA and protein:decreased expression:anterior temporal lobeRGD 
Ephb4Rathemangiopericytoma  ISOEPHB4 (Homo sapiens)mRNA and protein:decreased expression:anterior temporal lobeRGD 
Ephb4Mousehemangiopericytoma  ISOEPHB4 (Homo sapiens)mRNA and protein:decreased expression:anterior temporal lobeRGD 
HES1Humanhemangiopericytoma  IEP mRNA:increased expression:anterior temporal lobeRGD 
HEY1Humanhemangiopericytoma  IEP mRNA and protein:increased expression:anterior temporal lobeRGD 
HEY2Humanhemangiopericytoma  IEP mRNA:increased expression:anterior temporal lobeRGD 
Hes1Rathemangiopericytoma  ISOHES1 (Homo sapiens)mRNA:increased expression:anterior temporal lobeRGD 
Hes1Mousehemangiopericytoma  ISOHES1 (Homo sapiens)mRNA:increased expression:anterior temporal lobeRGD 
Hey1Rathemangiopericytoma  ISOHEY1 (Homo sapiens)mRNA and protein:increased expression:anterior temporal lobeRGD 
Hey1Mousehemangiopericytoma  ISOHEY1 (Homo sapiens)mRNA and protein:increased expression:anterior temporal lobeRGD 
Hey2Rathemangiopericytoma  ISOHEY2 (Homo sapiens)mRNA:increased expression:anterior temporal lobeRGD 
Hey2Mousehemangiopericytoma  ISOHEY2 (Homo sapiens)mRNA:increased expression:anterior temporal lobeRGD 
KDRHumanhemangiopericytoma  IEP mRNA:increased expression:anterior temporal lobeRGD 
KdrRathemangiopericytoma  ISOKDR (Homo sapiens)mRNA:increased expression:anterior temporal lobeRGD 
KdrMousehemangiopericytoma  ISOKDR (Homo sapiens)mRNA:increased expression:anterior temporal lobeRGD 
NOTCH1Humanhemangiopericytoma  IEP mRNA and protein:increased expression:anterior temporal lobeRGD 
NOTCH4Humanhemangiopericytoma  IEP mRNA and protein:increased expression:anterior temporal lobeRGD 
Notch1Rathemangiopericytoma  ISONOTCH1 (Homo sapiens)mRNA and protein:increased expression:anterior temporal lobeRGD 
Notch1Mousehemangiopericytoma  ISONOTCH1 (Homo sapiens)mRNA and protein:increased expression:anterior temporal lobeRGD 
Notch4Rathemangiopericytoma  ISONOTCH4 (Homo sapiens)mRNA and protein:increased expression:anterior temporal lobeRGD 
Notch4Mousehemangiopericytoma  ISONOTCH4 (Homo sapiens)mRNA and protein:increased expression:anterior temporal lobeRGD 
PTENHumanhemangiopericytoma  IEP protein:decreased expression:anterior temporal lobeRGD 
PtenRathemangiopericytoma  ISOPTEN (Homo sapiens)protein:decreased expression:anterior temporal lobeRGD 
PtenMousehemangiopericytoma  ISOPTEN (Homo sapiens)protein:decreased expression:anterior temporal lobeRGD 

Objects Annotated

Genes (Rattus norvegicus)
Dll4  (delta like canonical Notch ligand 4)
Ephb4  (EPH receptor B4)
Hes1  (hes family bHLH transcription factor 1)
Hey1  (hes-related family bHLH transcription factor with YRPW motif 1)
Hey2  (hes-related family bHLH transcription factor with YRPW motif 2)
Kdr  (kinase insert domain receptor)
Notch1  (notch receptor 1)
Notch4  (notch receptor 4)
Pten  (phosphatase and tensin homolog)

Genes (Mus musculus)
Dll4  (delta like canonical Notch ligand 4)
Ephb4  (Eph receptor B4)
Hes1  (hes family bHLH transcription factor 1)
Hey1  (hairy/enhancer-of-split related with YRPW motif 1)
Hey2  (hairy/enhancer-of-split related with YRPW motif 2)
Kdr  (kinase insert domain protein receptor)
Notch1  (notch 1)
Notch4  (notch 4)
Pten  (phosphatase and tensin homolog)

Genes (Homo sapiens)
DLL4  (delta like canonical Notch ligand 4)
EPHB4  (EPH receptor B4)
HES1  (hes family bHLH transcription factor 1)
HEY1  (hes related family bHLH transcription factor with YRPW motif 1)
HEY2  (hes related family bHLH transcription factor with YRPW motif 2)
KDR  (kinase insert domain receptor)
NOTCH1  (notch receptor 1)
NOTCH4  (notch receptor 4)
PTEN  (phosphatase and tensin homolog)


Additional Information