Display Settings:

Format

Send to:

Choose Destination
See comment in PubMed Commons below
Cancer Biol Ther. 2010 Feb;9(3):176-82. Epub 2010 Feb 16.

Targeting pericytes with a PDGF-B aptamer in human ovarian carcinoma models.

Author information

  • 1Department of Gynecologic Oncology, U.T.M.D. Anderson Cancer Center, Houston, TX, USA.

Abstract

PURPOSE:

On the basis of the known role of platelet-derived growth factor (PDGF)-BB/PDGF receptor (PDGFR) beta in pericyte regulation, highly specific inhibitors of this target are needed. We tested the efficacy of a highly selective aptamer against PDGF-B with or without anti-VEGF therapy in ovarian cancer models.

RESULTS:

Bevacizumab inhibited tumor growth by 45% and 48% in the HeyA8 and SKOV3ip1 models, respectively. AX102 had minimal effect on the HeyA8 model, but increased tumor growth in the SKOV3ip1 model. However, bevacizumab plus AX102 was more effective than bevacizumab alone, and resulted in 76-88% inhibition of tumor growth in both models. A longitudinal study in the HeyA8 model using bioluminescence imaging showed that combination of bevacizumab, AX102 and paclitaxel caused tumor reduction by 65% (based on bioluminescence imaging). In the HeyA8 model, MVD and PCNA counts were significantly reduced in the bevacizumab treatment groups, and pericyte coverage was significantly decreased in the AX102 treatment groups. In the SKOV3ip1 model, MVD and PCNA was significantly reduced in the bevacizumab treatment group, and even lower in the bevacizumab and AX102 combination treatment group.

EXPERIMENTAL DESIGN:

The therapeutic efficacy of targeting endothelial cells (bevacizumab) and/or pericytes (PDGF-aptamer, AX102) was examined using HeyA8 and SKOV3ip1 orthotopic models of ovarian cancer metastasis. Following therapy, tumors were examined for microvessel density (MVD), proliferating cell nuclear antigen (PCNA) and vascular maturation (pericyte coverage).

CONCLUSIONS:

Dual targeting of endothelial cells and pericytes holds potential as an anti-vascular therapeutic approach in ovarian carcinoma.

Comment in

PMID:
20009575
[PubMed - indexed for MEDLINE]
PMCID:
PMC3155813
Free PMC Article

Images from this publication.See all images (3)Free text

Figure 1
Figure 2
Figure 3

Publication Types, MeSH Terms, Substances, Grant Support

Publication Types

MeSH Terms

Substances

Grant Support

PubMed Commons home

PubMed Commons

0 comments
How to join PubMed Commons

    Supplemental Content

    Icon for Landes Bioscience Icon for PubMed Central
    Loading ...
    Write to the Help Desk