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Biologic effects of platelet-derived growth factor receptor α blockade in uterine cancer.

Publication ,  Journal Article
Roh, J-W; Huang, J; Hu, W; Yang, X; Jennings, NB; Sehgal, V; Sohn, BH; Han, HD; Lee, SJ; Thanapprapasr, D; Bottsford-Miller, J; Zand, B ...
Published in: Clin Cancer Res
May 15, 2014

PURPOSE: Platelet-derived growth factor receptor α (PDGFRα) expression is frequently observed in many kinds of cancer and is a candidate for therapeutic targeting. This preclinical study evaluated the biologic significance of PDGFRα and PDGFRα blockade (using a fully humanized monoclonal antibody, 3G3) in uterine cancer. EXPERIMENTAL DESIGN: Expression of PDGFRα was examined in uterine cancer clinical samples and cell lines, and biologic effects of PDGFRα inhibition were evaluated using in vitro (cell viability, apoptosis, and invasion) and in vivo (orthotopic) models of uterine cancer. RESULTS: PDGFRα was highly expressed and activated in uterine cancer samples and cell lines. Treatment with 3G3 resulted in substantial inhibition of PDGFRα phosphorylation and of downstream signaling molecules AKT and mitogen-activated protein kinase (MAPK). Cell viability and invasive potential of uterine cancer cells were also inhibited by 3G3 treatment. In orthotopic mouse models of uterine cancer, 3G3 monotherapy had significant antitumor effects in the PDGFRα-positive models (Hec-1A, Ishikawa, Spec-2) but not in the PDGFRα-negative model (OVCA432). Greater therapeutic effects were observed for 3G3 in combination with chemotherapy than for either drug alone in the PDGFRα-positive models. The antitumor effects of therapy were related to increased apoptosis and decreased proliferation and angiogenesis. CONCLUSIONS: These findings identify PDGFRα as an attractive target for therapeutic development in uterine cancer.

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Published In

Clin Cancer Res

DOI

EISSN

1557-3265

Publication Date

May 15, 2014

Volume

20

Issue

10

Start / End Page

2740 / 2750

Location

United States

Related Subject Headings

  • Xenograft Model Antitumor Assays
  • Uterine Neoplasms
  • Transcriptome
  • Signal Transduction
  • Receptor, Platelet-Derived Growth Factor alpha
  • Proto-Oncogene Proteins c-akt
  • Phosphorylation
  • Oncology & Carcinogenesis
  • Oligonucleotide Array Sequence Analysis
  • Neovascularization, Pathologic
 

Citation

APA
Chicago
ICMJE
MLA
NLM
Roh, J.-W., Huang, J., Hu, W., Yang, X., Jennings, N. B., Sehgal, V., … Sood, A. K. (2014). Biologic effects of platelet-derived growth factor receptor α blockade in uterine cancer. Clin Cancer Res, 20(10), 2740–2750. https://doi.org/10.1158/1078-0432.CCR-13-2507
Roh, Ju-Won, Jie Huang, Wei Hu, XiaoYun Yang, Nicholas B. Jennings, Vasudha Sehgal, Bo Hwa Sohn, et al. “Biologic effects of platelet-derived growth factor receptor α blockade in uterine cancer.Clin Cancer Res 20, no. 10 (May 15, 2014): 2740–50. https://doi.org/10.1158/1078-0432.CCR-13-2507.
Roh J-W, Huang J, Hu W, Yang X, Jennings NB, Sehgal V, et al. Biologic effects of platelet-derived growth factor receptor α blockade in uterine cancer. Clin Cancer Res. 2014 May 15;20(10):2740–50.
Roh, Ju-Won, et al. “Biologic effects of platelet-derived growth factor receptor α blockade in uterine cancer.Clin Cancer Res, vol. 20, no. 10, May 2014, pp. 2740–50. Pubmed, doi:10.1158/1078-0432.CCR-13-2507.
Roh J-W, Huang J, Hu W, Yang X, Jennings NB, Sehgal V, Sohn BH, Han HD, Lee SJ, Thanapprapasr D, Bottsford-Miller J, Zand B, Dalton HJ, Previs RA, Davis AN, Matsuo K, Lee J-S, Ram P, Coleman RL, Sood AK. Biologic effects of platelet-derived growth factor receptor α blockade in uterine cancer. Clin Cancer Res. 2014 May 15;20(10):2740–2750.

Published In

Clin Cancer Res

DOI

EISSN

1557-3265

Publication Date

May 15, 2014

Volume

20

Issue

10

Start / End Page

2740 / 2750

Location

United States

Related Subject Headings

  • Xenograft Model Antitumor Assays
  • Uterine Neoplasms
  • Transcriptome
  • Signal Transduction
  • Receptor, Platelet-Derived Growth Factor alpha
  • Proto-Oncogene Proteins c-akt
  • Phosphorylation
  • Oncology & Carcinogenesis
  • Oligonucleotide Array Sequence Analysis
  • Neovascularization, Pathologic